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Vascular function serves as a prognostic marker for cardiovascular disease and may exhibit seasonal variations due to lifestyle and environmental factors. Our systematic review aimed to determine whether seasonal variations in vascular function are present. We conducted a search of five databases (MEDLINE via PubMed, CINAHL, Web of Science, Cochrane Library, and Biomed Central) to identify evidence of seasonal variations in vascular function. Studies were eligible for inclusion if they assessed vascular function in adult humans during two or more seasons and were published in English. Of the 20,420 studies screened, 12 were eligible and none were excluded due to bias. Nine studies reported significant seasonal variations in vascular function, whereas three studies found no significant seasonal variations. The seasonality of vascular function remains unclear. However, current literature indicates that vascular dysfunction may exhibit a seasonal pattern, with vascular function reduced in the winter. Seasonal variations in endothelial function necessitate further exploration, particularly concerning factors such as exercise, temperature, light exposure, and air pollution. Future research should adopt standardised protocols, involve diverse and larger populations, employ longitudinal designs to minimise confounding factors, systematically measure and adjust for environmental variables, and accurately assess the impact of seasonal variation on vascular function. [ABSTRACT FROM AUTHOR]

ABSTRACT Arterial stiffness is a significant predictor of cardiovascular disease and mortality. Physical activity (PA) has been extensively studied for its potential to reduce arterial stiffness, but the relationship between different types, durations, and intensities of PA and arterial stiffness remains a topic of ongoing research. Therefore, in this narrative review, we evaluated the current evidence focusing on the effect of PA on arterial stiffness and vascular health and discussed the known underlying physiological mechanisms. PA, irrespective of its intensity or pattern, is consistently associated with lower arterial stiffness. Aerobic exercise, particularly at higher intensities, is the most effective strategy for reducing arterial stiffness. These benefits are especially significant in populations with higher cardiovascular risk, such as those with type 2 diabetes mellitus and hypertension. Therefore, maintaining an active lifestyle into older age is crucial for vascular health and may contribute to healthy aging. [ABSTRACT FROM AUTHOR]

Alarmins are classified by their release from damaged or ruptured cells. Many alarmins have been found to increase vascular tone and oppose endothelium‐dependent dilatation (EDD). Interleukin (IL)‐33 plays a prominent role in lung injury and can be released during vascular injury and in chronic studies found to be cardioprotective. Our recent work has implicated IL‐33 in acute vascular dysfunction following inhalation of engineered nanomaterials (ENM). However, the mechanisms linking IL‐33 to vascular tone have not been interrogated. We therefore aimed to determine whether IL‐33 directly influenced microvascular tone and endothelial function. Isolated feed arteries and in vivo arterioles from male and female Sprague–Dawley rats were used to determine direct vascular actions of IL‐33. Mesenteric feed arteries and arterioles demonstrated reduced intraluminal diameters when treated with increasing concentrations of recombinant IL‐33. IL‐33 activated extracellular signal regulated kinase (ERK)1/2 of rat aortic smooth muscle cells but not phosphorylation of myosin light chain kinase. This suggested IL‐33 may sensitize arterioles to Ca2+‐mediated responses. Indeed, IL‐33 augmented the myogenic‐ and phenylephrine‐induced vasoconstriction. Additionally, incubation of arterioles with 1 ng IL‐33 attenuated ACh‐mediated EDD. Mechanistically, in human aortic endothelial cells, we demonstrate that IL‐33‐mediated ERK1/2 activation leads to inhibitory phosphorylation of serine 602 on endothelial nitric oxide synthase. Finally, we demonstrate that IL‐33‐ERK1/2 contributes to vascular tone following two known inducers of IL‐33; ENM inhalation and the rupture endothelial cells. The present study provides novel evidence that IL‐33 increases vascular tone via canonical ERK1/2 activation in microvascular smooth muscle and endothelium. Altogether, it is suggested IL‐33 plays a critical role in microvascular homeostasis following barrier cell injury. Key points: Interleukin (IL)‐33 causes a concentration‐dependent reduction in feed artery diameter.IL‐33 acts on vascular smooth muscle cells to augment Ca2+‐mediated processes.IL‐33 causes inhibitory phosphorylation of endothelial nitric oxide synthase and opposes endothelium‐dependent dilatation.Engineered nanomaterial‐induced lung injury and endothelial cell rupture in part act through IL‐33 to mediate increased vascular tone. [ABSTRACT FROM AUTHOR]

Background: Night shift workers face increased risk of cardiovascular disease (CVD) compared to non-shift workers. Evidence supports on-shift napping and regular non-invasive monitoring of endothelial function for risk mitigation, yet neither strategy is widely used. Methods: We evaluated the feasibility of non-invasive assessment of peripheral arterial tone (PAT) to assess the effect of napping during simulated night shift work on endothelial function. We used a single-site, randomized crossover trial of simulated night shift work with a 45-min nap condition versus a control, no-nap condition (ClinicalTrials.gov NCT05436951). Results: The primary outcome was the number of participants with ≥ 70% of endothelial function assessments. Secondary outcomes included mean reactive hyperemia index (RHI), BP, and cognitive performance with the brief psychomotor vigilance task (PVT-B). Of the 10 consented, 9 completed both conditions. All participants exceeded feasibility benchmarks. Mean RHI did not differ by nap condition, and the delta from pre- to post measure did not differ (difference in delta = − 0.26, 95% CI − 1.09, 0.58). Hourly PVT-B assessments from 19:00 to 07:00 h did not differ by nap condition. Compared to pre-nap measures, cognitive performance on the PVT-B was poorest at + 0 min post-nap. Conclusion: Our findings can inform larger studies evaluating the effects of night shift work and napping on endothelial function. Trial registrations: ClinicalTrials.gov (NCT05436951, registered on June 23, 2022). [ABSTRACT FROM AUTHOR]

Vascular dysfunction, marked by lower endothelial function and increased aortic stiffness, is a nontraditional risk factor that precedes the development of cardiovascular disease (CVD). However, the age at which these changes in vascular function occur in women and the degree to which reproductive hormones mediate these changes has not been characterized. Women free from major disease were enrolled across the adult life span (aged 18–70 yr, n = 140). Endothelial function was assessed as flow-mediated dilation (FMD) of the brachial artery during reactive hyperemia using duplex ultrasound and expressed as percent dilation. Aortic stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). Blood samples were obtained to quantify reproductive hormone concentration. Regression models determined age-related breakpoints and mediating factors between age and vascular outcomes. FMD declined with age with a breakpoint and steeper decline occurring at 47 yr of age. Thereafter, age was independently associated with lower FMD (B = −0.13, P < 0.001). cfPWV was relatively stable until a breakpoint at age 48, and age was independently associated with higher cfPWV thereafter (B = 0.10, P < 0.001). Path analysis revealed that the association between age and FMD was partially mediated by follicle-stimulating hormone (abind = 0.051, P = 0.01) and progesterone (abind = 0.513, P < 0.001) but not estradiol (abind = −0.004, P = 0.08). No mediation was present for cfPWV. Age was associated with endothelial dysfunction and aortic stiffness in women beginning at 47 and 48 yr old, respectively, 3 to 4 yr before the average age of menopause. The association between age and endothelial dysfunction was explained in part by elevations in follicle-stimulating hormone and progesterone, but not declining estradiol. NEW & NOTEWORTHY: We demonstrate that the age at which endothelial function declines and aortic stiffness increases in healthy women is 47 and 48, respectively. The inflection point in flow-mediated dilation (FMD) is 6 yr earlier than previously reported, and the association between age and FMD was mediated by follicle-stimulating hormone (FSH) and progesterone (P4) but not estradiol (E2). [ABSTRACT FROM AUTHOR]

Ischaemic preconditioning (IPC), brief periods of ischaemia immediately followed by reperfusion applied to a vascular bed, has emerged as a method to improve exercise performance. There is, however, a lack of research exploring repeated episodes of IPC on anaerobic performance. The aim of this study was to determine if a 2-week repeated IPC intervention could enhance anaerobic performance in male academy football players. Eight male academy football players completed two, 2-week intervention trials: six IPC episodes (4 × 5 min at 220 mmHg per episode), and six SHAM episodes (4 × 5 min at 20 mmHg per episode). Prior to and following each intervention trial, the participants completed assessments of anaerobic performance (Running Anaerobic Sprint Test [RAST]), and superficial femoral artery endothelial function (flow-mediated dilation [FMD]). IPC significantly enhanced peak and mean power output by 12% (p = 0.026) and 11% (p = 0.019) and significantly improved superficial femoral artery FMD (p = 0.049). The increase in endothelial function suggests that this may be a mechanism contributing to this enhancement of anaerobic performance. The present study supports the use of repeated IPC prior to matches and training sessions to enhance anaerobic performance. [ABSTRACT FROM AUTHOR]

There is no study that has investigated the impact of exercise in a combined hypoxic and hot environment on endothelial function. Therefore, we tested whether aerobic exercise in a combined hypoxic and hot conditions induces further enhancement of endothelial function. Twelve healthy males cycled at a constant workload (50% of their maximal oxygen uptake under normoxic/thermoneutral conditions) for 30 min in four different environments: exercise under normoxic condition (NOR: fraction of inspiratory oxygen or FiO2 = 20.9%, 20°C), exercise under hypoxic condition (HYP: FiO2 = 14.5%, 20°C), exercise under hot condition (HOT: FiO2 = 20.9%, 30°C), and exercise under combined hypoxia and hot conditions (HH: FiO2 = 14.5%, 30°C). Before, during, and after exercise, cardiovascular variables (e.g., heart rate, blood flow, and shear rate), blood variables, and endothelial function evaluated by flow‐mediated dilation (FMD) were assessed. Heart rates were significantly higher throughout the HH trial's experimental period than the other trials (p < 0.05). However, in the HH trial, brachial artery blood flow and shear rate did not differ from those in other trials after exercise. Plasma catecholamines (epinephrine, norepinephrine, and dopamine) elevations in response to exercise were significantly higher in the HH trial than in the other three trials (p < 0.05). No considerable differences were observed in FMD responses among trials before and after the exercise. In conclusion, aerobic exercise in a combined hot and hypoxic environment further activated sympathetic nervous activity but did not considerably enhance blood flow, shear rate, or endothelial function. [ABSTRACT FROM AUTHOR]

Background and Purpose: Remote ischaemic preconditioning (rIPC) for cardioprotection is severely impaired in diabetes, and therapeutic options to restore it are lacking. The vascular endothelium plays a key role in rIPC. Given that the activity of endothelial nitric oxide synthase (eNOS) is inhibited by proline‐rich tyrosine kinase 2 (Pyk2), we hypothesized that pharmacological Pyk2 inhibition could restore eNOS activity and thus restore remote cardioprotection in diabetes. Experimental Approach: New Zealand obese (NZO) mice that demonstrated key features of diabetes were studied. The consequence of Pyk2 inhibition on endothelial function, rIPC and infarct size after myocardial infarction were evaluated. The impact of plasma from mice and humans with or without diabetes was assessed in isolated buffer perfused murine hearts and aortic rings. Key Results: Plasma from nondiabetic mice and humans, both subjected to rIPC, caused remote tissue protection. Similar to diabetic humans, NZO mice demonstrated endothelial dysfunction. NZO mice had reduced circulating nitrite levels, elevated arterial blood pressure and a larger infarct size after ischaemia and reperfusion than BL6 mice. Pyk2 increased the phosphorylation of eNOS at its inhibitory site (Tyr656), limiting its activity in diabetes. The cardioprotective effects of rIPC were abolished in diabetic NZO mice. Pharmacological Pyk2 inhibition restored endothelial function and rescued cardioprotective effects of rIPC. Conclusion and Implications: Endothelial function and remote tissue protection are impaired in diabetes. Pyk2 is a novel target for treating endothelial dysfunction and restoring cardioprotection through rIPC in diabetes. [ABSTRACT FROM AUTHOR]

This study examines the impact of mung bean (Vigna radiata) protein consumption on endothelial function in middle-aged adults, focusing on antioxidant enzyme activity and anti-inflammatory markers. Mung beans have shown promise in enhancing cardiovascular function, lowering blood pressure, and improving lipid profiles, but the underlying mechanisms of these functions remain unclear. Conducted as a three-arm randomized, double-blind, placebo-controlled trial, this study involved male and female participants aged 45 to 60 and assigned them to consume either a placebo or a mung bean functional drink containing 10 or 15 g of mung bean protein daily for six weeks. Vasodilation was assessed using flow-mediated dilation (FMD), and oxidative stress markers, antioxidant enzyme activity, and inflammatory markers were measured at baseline and after the intervention. The results indicate that six weeks of mung bean consumption significantly benefits healthy middle-aged adults by enhancing antioxidant enzyme activity and reducing inflammatory mediators' expression. Additionally, the increase in brachial artery diameter following FMD indicates improved endothelial function. [ABSTRACT FROM AUTHOR]

Background: Severe COVID-19 is associated with neutrophilic inflammation and immunothrombosis. Several members of the IL-17 cytokine family have been associated with neutrophilic inflammation and activation of the endothelium. Therefore, we investigated whether these cytokines were associated with COVID-19. Methods: We investigated the association between COVID-19 and circulating plasma levels of IL-17 cytokine family members in participants to the Biobanque québécoise de la COVID-19 (BQC19), a prospective observational cohort and an independent cohort from Western University (London, Ontario). We measured the in vitro impact of IL-17F on intercellular adhesion molecule 1 (ICAM-1) cell surface expression and neutrophil adhesion on endothelial cells in culture. The contribution of two Mitogen Activated Protein Kinase (MAPK) pathways was determined using small molecule inhibitors PD184352 (a MKK1/MKK2 inhibitor) and BIRB0796 (a p38 MAPK inhibitor). Results: We found increased IL-17D and IL-17F plasma levels when comparing SARS-CoV-2-positive vs negative hospitalized participants. Moreover, increased plasma levels of IL-17D, IL-17E and IL-17F were noted when comparing severe versus mild COVID-19. IL-17F, but not IL-17A, was significantly elevated in people with COVID-19 compared to healthy controls and with more severe disease. In vitro work on endothelial cells treated with IL-17F for 24h showed an increase cell surface expression of ICAM-1 accompanied by neutrophil adhesion. The introduction of two MAPK inhibitors significantly reduced the binding of neutrophils while also reducing ICAM-1 expression at the surface level of endothelial cells, but not its intracellular expression. Discussion: Overall, these results have identified an association between two cytokines of the IL-17 family (IL-17D and IL-17F) with COVID-19 and disease severity. Considering that IL-17F stimulation promotes neutrophil adhesion to the endothelium in a MAPK-dependent manner, it is attractive to speculate that this pathway may contribute to pathogenic immunothrombosis in concert with other molecular effectors. [ABSTRACT FROM AUTHOR]

Background Results Conclusion Semaglutide, a glucagon‐like peptide‐1 (GLP‐1) receptor agonist, is a widely used drug for the treatment of type 2 diabetes that offers significant cardiovascular benefits.This review systematically examines the proteomic and metabolomic indicators associated with the cardiovascular effects of semaglutide. A comprehensive literature search was conducted to identify relevant studies. The review utilizes advanced analytical technologies such as mass spectrometry and nuclear magnetic resonance (NMR) to investigate the molecular mechanisms underlying the effects of semaglutide on insulin secretion, weight control, anti‐inflammatory activities and lipid metabolism. These “omics” approaches offer critical insights into metabolic changes associated with cardiovascular health. However, challenges remain such as individual variability in expression, the need for comprehensive validation and the integration of these data with clinical parameters. These issues need to be addressed through further research to refine these indicators and increase their clinical utility.Future integration of proteomic and metabolomic data with artificial intelligence (AI) promises to improve prediction and monitoring of cardiovascular outcomes and may enable more accurate and effective management of cardiovascular health in patients with type 2 diabetes. This review highlights the transformative potential of integrating proteomics, metabolomics and AI to advance cardiovascular medicine and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Objective To analyze the effects of agatroban combined with mitochondrial transplantation on endothelial function and hemorheology in mice with cerebral ischemia-reperfusion injury. Methods 50 SPF grade Kunming mice, with 10 as the normal group, 38 mices were successfully modeled and divided into a model group of 9, a mitochondrial transplantation group of 9, an Agatroban group of 10, and a combination group of 10. The mitochondrial transplantation group was given exogenous mitochondrial extract, the agatroban group was given agatroban, the combined group was given agatroban combined with mitochondrial transplantation, and the blank group and model group were injected with normal saline. Observation of changes in cerebral infarction volume, pathological morphology of brain tissue, endothelial function, hemorheology, and relative expression of apoptosis related proteins in mice after 7 days of intervention. Results Compared with normal group, cerebral infarction volume ratio, ET-1, whole blood viscosity, plasma viscosity, Caspase-3 and Bax protein expression levels were increased in model group, mitochondrial transplantation group, agatroban group and combined group, while NO level and Bcl-2 protein expression levels were decreased (P < 0.05). Compared with the model group, the cerebral infarction volume ratio, ET-1, whole blood viscosity, plasma viscosity, Caspase-3 and Bax protein expressions in the mitochondrial transplantation group, agatroban group and combined group were decreased, and the combined group was lower than the mitochondrial transplantation group and agatroban group, and the NO level and Bcl-2 protein expression were increased. The combined group was higher than that of mitochondrial transplantation group and agatriban group (P < 0.05). Conclusion In mice with cerebral ischemia-reperfusion injury, endothelial function injury was improved, hemorheology was regulated, and brain injury was alleviated after agatroban combined with mitochondrial transplantation. [ABSTRACT FROM AUTHOR]

Introduction: Endothelial dysfunction (ED) promotes the development of atherosclerosis, and studies suggest an association with age-related neurocognitive disorders. It is currently unclear whether ED is also associated with the risk of perioperative neurocognitive disorders. Method: We included 788 participants aged ≥ 65 years of the BioCog study. Patients were scheduled to undergo elective surgery with expected duration > 60 min. Blood was collected before surgery for measurement of 5 biomarkers of ED: asymmetric and symmetric dimethylarginine (ADMA; SDMA), intercellular and vascular adhesion molecule (ICAM-1, VCAM-1), and von Willebrand factor (vWF). Patients were monitored for the occurrence of postoperative delirium (POD) daily until the 7th postoperative day. 537 (68.1%) patients returned for a 3-month follow-up. Post-operative cognitive dysfunction (POCD) was defined from the change in results on a battery of 6 neuropsychological tests between baseline and 3 months, compared to the change in results of a control group during the 3-month interval. The associations of each of the 5 ED biomarkers with POD and POCD respectively were determined using multiple logistic regression analyses with adjustment for age, sex, surgery type, pre-morbid IQ, body mass index, hypertension, diabetes, HbA1C, triglyceride, total and HDL cholesterol. Results: 19.8% of 788 patients developed POD; 10.1% of 537 patients had POCD at 3 months. Concentrations of ED biomarkers were not significantly associated with a POD. A higher VCAM-1 concentration was associated with a reduced POCD risk (adjusted odds ratio 0.55; 95% CI: 0.35–0.86). No further statistically significant results were found. Conclusion: Pre-operative concentrations of ED biomarkers were not associated with POD risk. We unexpectedly found higher VCAM-1 to be associated with a reduced POCD risk. Further studies are needed to evaluate these findings. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of dobutamine combined with anisodamine hydrobromide on endothelial function and immune function in patients with septic shock. A total of 100 patients with septic shock admitted from January 2023 to January 2024 were randomly divided into control group and observation group, with 50 cases each. The control group was given dobutamine and normal saline, and the observation group was given dobutamine and anisodaminehydrobromide. After treatment, compared with the observation group, the levels of TNF-α, CRP, IL-6, PCT, VO2, O2ER, E-SLT, sTM, ET-1, Ang-2 and CD8+ in the control group were all increased, while the levels of ScvO2, DO2, CD4+, CD3+ and CD4+/CD8+ were decreased. There was statistical difference (P<0.05). In addition, the length of hospital stay, time of getting out of bed and duration of shock in control group were significantly higher than those in observation group, while the total clinical effective rate was lower than that in observation group (P<0.05). Statistical difference between the two groups (P>0.05). Dobutamine combined with anisodamine hydrobromide can improve the endothelial function, clear the inflammatory mediators, improve immune function, and reduce the incidence of complications on septic shock patients, which has clinical application value. [ABSTRACT FROM AUTHOR]

Background: Obstructive Sleep Apnea (OSA) is characterized by repeated episodes of partial or complete obstruction of the upper airway during sleep, leading to cardiovascular complications due to endothelial dysfunction. Understanding how OSA affects endothelial function compared to healthy individuals can provide insights into preventive strategies. Objective: This study aims to assess and compare endothelial function in patients with obstructive sleep apnea versus healthy sleepers. Methods: We conducted a cross-sectional study with 50 patients diagnosed with obstructive sleep apnea and 50 healthy sleepers matched by age and sex. Endothelial function was assessed using flow-mediated dilation (FMD) measured by ultrasound of the brachial artery. Results: The study is expected to reveal significant differences in endothelial function between patients with obstructive sleep apnea and healthy sleepers, contributing to the understanding of cardiovascular risks associated with OSA. Conclusion: Assessing endothelial function in these populations can provide valuable information for cardiovascular risk assessment and the potential benefits of therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective: Gestational diabetes mellitus (GDM) and preeclampsia are the most common medical complications of pregnancy. Both GDM and preeclampsia are risk factors for cardiovascular diseases (CVD) and atherosclerosis. Flow-mediated dilatation (FMD) is a good ultrasonographic marker of early atherosclerotic changes used to measure endothelial function. In this study; we evaluated FMD, an indicator of endothelial function, and investigated whether there was an increased risk of CVD in patients with a history of preeclampsia or GDM. Methods: The study was carried out with 104 patients who gave birth in the Obstetrics and Gynecology Clinic of Bolu Abant İzzet Baysal University Training and Research Hospital between January 2016 and January 2017. Thirty four patients with a history of preeclampsia, 37 patients with a history of GDM, and 33 patients with uncomplicated deliveries were included in the study. All patients in the study had only one live birth and their age range was between 20 and 30 years. Demographic data, cardiovascular risk markers, obstetric data, laboratory tests and FMD change (%) measurements of all patients were compared. Mean and standard deviation values of the obtained data were calculated. Results: The mean FMD change (%) in the group of patients with a history of preeclampsia was 9.8±3.1. It was 10.32±2.50 in the group of patients with a history of GDM and it was 13.19±3.03 in the control group. A statistically significant difference was found between the control group and GDM and preeclampsia groups in terms of FMD change (%) (<0.001). There was a significant negative correlation between FMD change (%) and systolic blood pressure, diastolic blood pressure, the amount of proteinuria, and glucose, low-density lipoprotein and total cholesterol levels. Conclusion: The use of FMD change (%) measurement in patients with a history of GDM and preeclampsia can be used as a predictive marker for CVD, and early detection of risk can be time-consuming in terms of prevention. Demonstrating that GDM and preeclampsia cause increased cardiovascular risk in women's lives will raise awareness of taking measures to reduce the risk in this group of patients. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is associated with subclinical atherosclerosis and endothelial dysfunction, which can be assessed non-invasively through flow-mediated dilation (FMD). In this study, we evaluated the potential impact of inhaled corticosteroid (ICS) therapy on FMD of COPD patients undergoing pulmonary rehabilitation (PR). Methods: Medical records of COPD patients undergoing FMD assessment upon admission to our Pulmonary Rehabilitation Unit were reviewed in this retrospective post hoc analysis. Results: A total of 46 patients with COPD (median age 71.5 years, 28.3% postmenopausal females) were included in the final analysis. Among these, 27 participants were currently receiving ICS therapy, while 19 were not. At baseline, the two groups showed no difference in the main clinical and functional variables. Similarly, no significant difference was observed in vascular reactivity parameters, with a median FMD of 3.12% (IQR: 2.23–4.45) in ICS users and 3.39% (IQR: 2.45–4.08) in ICS nonusers (p = 0.544). After PR, a significant improvement in the main rehabilitation and patient-reported outcomes was observed in all groups, with a significant improvement in FMD documented in both patients treated with steroids (from 3.12%; IQR: 2.23–4.45 to 4.77%; IQR: 3.25–5.63, p = 0.022) and in those who were not (from 3.39%; IQR: 2.45–4.08 to 5.04%; IQR: 3.98–6.06, p = 0.005). FMD changes were of comparable magnitude among groups. Conclusions: Our preliminary findings do not indicate a significant impact of medications containing ICS on the endothelial function of COPD patients, suggesting that the potential beneficial effect of PR on this surrogate marker of cardiovascular risk is independent of inhaled therapy. [ABSTRACT FROM AUTHOR]

Historical exclusion of females in research has been, in part, due to the perceived influence of natural menstrual (NAT) and oral contraceptive pill (OCP) cycles on vascular outcomes. NAT and OCP cycle phases may influence brachial artery (BA) endothelial function, however, findings are mixed. Minimal research has examined arterial stiffness, smooth muscle, and lower limb endothelial function. The purpose of this study was to investigate the influence of NAT and OCP cycles on cardiovascular outcomes and cellular regulation. Forty-nine premenopausal females (n = 17 NAT, n = 17 second generation OCP, n = 15 third generation OCP) participated in two randomized order visits in the low (LH, early follicular/placebo) and high (HH, midluteal/active) hormone cycle phases. BA and superficial femoral artery (SFA) endothelial function [flow-mediated dilation (FMD) test], smooth muscle function (nitroglycerine-mediated dilation test), and carotid and peripheral (pulse wave velocity) arterial stiffness were assessed. Cultured female human endothelial cells were exposed to participant serum for 24 h to examine endothelial nitric oxide synthase (eNOS) and estrogen receptor-α (ERα) protein content. BA FMD was elevated in the HH vs. LH phase, regardless of group (HH, 7.7 ± 3.5%; LH, 7.0 ± 3.3%; P = 0.02); however, allometric scaling for baseline diameter resulted in no phase effect (HH, 7.6 ± 2.6%; LH, 7.1 ± 2.6%; P = 0.052, d = 0.35). SFA FMD, BA, and SFA smooth muscle function, arterial stiffness, and eNOS and ERα protein content were unaffected. NAT and OCP phases examined have minimal influence on vascular outcomes and ERα-eNOS pathway, apart from a small effect on BA endothelial function partially explained by differences in baseline artery diameter. NEW & NOTEWORTHY: Comprehensive evaluation of the cardiovascular system in naturally cycling and second and third generation OCP users indicates no major influence of hormonal phases examined on endothelial function and smooth muscle function in the arteries of the upper and lower limbs, arterial stiffness, or underlying cellular mechanisms. Study findings challenge the historical exclusion of female participants due to potentially confounding hormonal cycles; researchers are encouraged to consider the hormonal environment in future study design. [ABSTRACT FROM AUTHOR]

Women with a history of gestational diabetes mellitus (GDM) have a significantly greater lifetime risk of developing cardiovascular disease and type 2 diabetes compared with women who had an uncomplicated pregnancy (HC). Microvascular endothelial dysfunction, mediated via reduced nitric oxide (NO)-dependent dilation secondary to increases in oxidative stress, persists after pregnancy complicated by GDM. We examined whether this microvascular dysfunction reduces insulin-mediated vascular responses in women with a history of GDM. We assessed in vivo microvascular endothelium-dependent vasodilator function by measuring cutaneous vascular conductance responses to graded infusions of acetylcholine (10−10–10−1 M) and insulin (10−8–10−4 M) in control sites and sites treated with 15 mM l -NAME [NG-nitro- l -arginine methyl ester; NO-synthase (NOS) inhibitor] or 5 mM l -ascorbate. We also measured protein expression of total endothelial NOS (eNOS), insulin-mediated eNOS phosphorylation, and endothelial nitrotyrosine in isolated endothelial cells from GDM and HC. Women with a history of GDM had reduced acetylcholine (P < 0.001)- and insulin (P < 0.001)-mediated dilation, and the NO-dependent responses to both acetylcholine (P = 0.006) and insulin (P = 0.006) were reduced in GDM compared with HC. Insulin stimulation increased phosphorylated eNOS content in HC (P = 0.009) but had no effect in GDM (P = 0.306). Ascorbate treatment increased acetylcholine (P < 0.001)- and insulin (P < 0.001)-mediated dilation in GDM, and endothelial cell nitrotyrosine expression was higher in GDM compared with HC (P = 0.014). Women with a history of GDM have attenuated microvascular vasodilation responses to insulin, and this attenuation is mediated, in part, by reduced NO-dependent mechanisms. Our findings further implicate increased endothelial oxidative stress in this microvascular insulin resistance. NEW & NOTEWORTHY: Women who have gestational diabetes during pregnancy are at a greater risk for cardiovascular disease and type 2 diabetes in the decade following pregnancy. The mechanisms mediating this increased risk are unclear. Herein, we demonstrate that insulin-dependent microvascular responses are reduced in women who had gestational diabetes, despite the remission of glucose intolerance. This reduced microvascular sensitivity to insulin may contribute to increased cardiovascular disease and type 2 diabetes risk in these women. [ABSTRACT FROM AUTHOR]

Excess sodium consumption contributes to arterial dysfunction in humans. The C57BL/6 strain of mice has been used to identify mechanisms by which arterial dysfunction occurs after excess sodium consumption. However, there are concerns that C57BL/6 mice have strain-specific resistance to high-sodium (HS) diet-induced hypertension. To address this concern, we performed a meta-analysis to determine if excess sodium consumption in C57BL/6 mice induces arterial dysfunction. Databases were searched for HS versus standard diet studies that measured arterial function [i.e., systolic blood pressure (BP), endothelium-dependent dilation (EDD), and central arterial stiffness] in C57BL/6 mice. A total of 39 studies were included, demonstrating that the HS condition resulted in higher systolic BP than control mice with a mean difference of 9.8 mmHg (95% confidence interval [CI] = [5.6, 14], P < 0.001). Subgroup analysis indicated that the systolic BP was higher in HS compared with the control condition when measured during night compared with daytime with telemetry (P < 0.001). We also identified that the difference in systolic BP between HS and control was ∼2.5-fold higher when administered through drinking water than through food (P < 0.001). A total of 12 studies were included, demonstrating that the HS condition resulted in lower EDD than control with a weighted mean difference of −12.0% (95% CI = [−20.0, −4.1], P = 0.003). It should be noted that there was considerable variability across studies with more than half of the studies showing no effect of the HS condition on systolic BP or EDD. In summary, excess sodium consumption elevates systolic BP and impairs EDD in C57BL/6 mice. NEW & NOTEWORTHY: C57BL/6 mice are perceived as resistant to high-sodium diet-induced arterial dysfunction. This meta-analysis demonstrates that excess sodium consumption elevates blood pressure and impairs endothelium-dependent dilation in C57BL/6 mice. Nighttime measurements show more pronounced blood pressure elevation. In addition, sodium administration via drinking water, compared with food, induces a greater blood pressure elevation. These findings may be influenced by outlier studies, as the majority of studies showed no adverse effect of excess sodium consumption on arterial function. [ABSTRACT FROM AUTHOR]

As the innermost monolayer of the vasculature, endothelial cells (ECs) serve as the interface for multiplex signal transduction. Directly exposed to blood-borne factors, both endogenous and exogenous, ECs actively mediate vascular homeostasis and represent a therapeutic target against cardiometabolic diseases. ECs act as the first-line gateway between gut-derived substances and vasculature. Additionally, ECs convert blood flow-exerted hemodynamic forces into downstream biochemical signaling to modulate vascular pathophysiology. Besides, ECs can sense other forms of stimuli, like cell extrusion, thermal stimulation, photostimulation, radiation, magnetic field, noise, and gravity. Future efforts are still needed to deepen our understanding on endothelial biology. [Display omitted] • ECs are interfaces for multiplex signal transduction in the vasculature. • ECs are gatekeepers between gut-derived substances and vasculature. • ECs convert hemodynamic forces to biochemical signals, mediating vasopathology. • ECs are sensitive to various environmental stimuli. [ABSTRACT FROM AUTHOR]

To compare the acute response of moderate intensity continuous exercise (MICE) vs moderate intensity interval exercise (MIIE) on endothelial function, post-exercise hypotension (PEH), and glycemia in type 2 diabetes (T2DM) with hypertension. Twelve T2DM (aged 52.8 ± 3.8 years old) patients with hypertension underwent a randomized cross-over study following isocaloric (200 kcal) protocols: (i) MICE: walk-jogging at 50% of VO 2 peak, (ii) MIIE session: walking – jogging (stimulus/recovery – 3:3 min each) at 60% of VO 2 peak followed by recovery at 40% of VO 2 peak, and (iii) control (CON): lying quietly in a supine position for 30 min. A generalized estimating equation was utilized to verify possible differences over time × session. The %FMD (Baseline: 3.59 ± 1.58 vs. 30 min: 6.73 ± 4.34) and the absolute FMD changed after MIIE (Baseline: 0.16 ± 0.10 vs. 30 min: 0.17 ± 0.14). Only absolute FMD changed after MIIE (Baseline: 0.14 ± 0.07 vs. 30 min: 0.16 ± 0.07). Besides, MIIE at 30 min provides higher absolute FMD values when compared to baseline from MICE and baseline, 30 min, and 60 min from control. Regarding blood pressure, no PEH statistical main effect was found. Finally, the glycemia changed at baseline vs. 30 min and 60 min after MIIE (210.5 ± 9.4 vs. 127.6 ± 10.0 and 120 ± 8.9), MICE (219.5 ± 12.7 vs. 125.2 ± 12.0 and 118.2 ± 11.6), and control sessions (215.9 ± 11.8 vs. 187.4 ± 11.2 and 172.6 ± 11.3 mg/dL, p < 0.05). However, MIIE and MICE showed higher decreases compared to the control. MIIE and MICE sessions are similar and effective exercise strategies to induce changes in endothelial function and glycemic responses in type-2 diabetics with hypertension. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a chronic vascular degenerative disease characterized by progressive segmental dilation of the abdominal aorta. The rupture of an AAA represents a leading cause of death in cardiovascular diseases. Despite numerous experimental and clinical studies examining potential drug targets and therapies, currently there are no pharmaceutical treatment to prevent AAA growth and rupture. Iron is an essential element in almost all living organisms and has important biological functions. Epidemiological studies have indicated that both iron deficiency and overload are associated with adverse clinical outcomes, particularly an increased risk of cardiovascular events. Recent evidence indicates that iron overload is involved in the pathogenesis of abdominal aortic aneurysms. In this review, we provide an overview of the role of iron overload in AAA progression and explore its potential pathological mechanisms. Although the exact molecular mechanisms of iron overload in the development of AAA remain to be elucidated, the inhibition of iron deposition may offer a promising strategy for preventing these aneurysms. [ABSTRACT FROM AUTHOR]

Aim: The primary endothelial NADPH oxidase isoform 4 (NOX4) is notably induced during hypoxia, with emerging evidence suggesting its vasoprotective role through H2O2 production. Therefore, we aimed to elucidate NOX4′s significance in endothelial function under hypoxia. Methods: Human vessels, in addition to murine vessels from Nox4−/− mice, were explored. On a functional level, Mulvany myograph experiments were performed. To obtain mechanistical insights, human endothelial cells were cultured under hypoxia with inhibitors of hypoxia-inducible factors. Additionally, endothelial cells were cultured under combined hypoxia and laminar shear stress conditions. Results: In human occluded vessels, NOX4 expression strongly correlated with prostaglandin I2 synthase (PTGIS). Hypoxia significantly elevated NOX4 and PTGIS expression and activity in human endothelial cells. Inhibition of prolyl hydroxylase domain (PHD) enzymes, which stabilize hypoxia-inducible factors (HIFs), increased NOX4 and PTGIS expression even under normoxic conditions. NOX4 mRNA expression was reduced by HIF1a inhibition, while PTGIS mRNA expression was only affected by the inhibition of HIF2a under hypoxia. Endothelial function assessments revealed hypoxia-induced endothelial dysfunction in mesenteric arteries from wild-type mice. Mesenteric arteries from Nox4−/− mice exhibited an altered endothelial function under hypoxia, most prominent in the presence of cyclooxygenase inhibitor diclofenac to exclude the impact of prostacyclin. Restored protective laminar shear stress, as it might occur after thrombolysis, angioplasty, or stenting, attenuated the hypoxic response in endothelial cells, reducing HIF1a expression and its target NOX4 while enhancing eNOS expression. Conclusions: Hypoxia strongly induces NOX4 and PTGIS, with a close correlation between both factors in occluded, hypoxic human vessels. This relationship ensured endothelium-dependent vasodilation under hypoxic conditions. Protective laminar blood flow restores eNOS expression and mitigates the hypoxic response on NOX4 and PTGIS. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S), a gas traditionally considered toxic, is now recognized as a vital endogenous signaling molecule with a complex physiology. This comprehensive study encompasses a systematic literature review that explores the intricate mechanisms underlying H2S-induced vasodilation. The vasodilatory effects of H2S are primarily mediated by activating ATP-sensitive potassium (K_ATP) channels, leading to membrane hyperpolarization and subsequent relaxation of vascular smooth muscle cells (VSMCs). Additionally, H2S inhibits L-type calcium channels, reducing calcium influx and diminishing VSMC contraction. Beyond ion channel modulation, H2S profoundly impacts cyclic nucleotide signaling pathways. It stimulates soluble guanylyl cyclase (sGC), increasing the production of cyclic guanosine monophosphate (cGMP). Elevated cGMP levels activate protein kinase G (PKG), which phosphorylates downstream targets like vasodilator-stimulated phosphoprotein (VASP) and promotes smooth muscle relaxation. The synergy between H2S and nitric oxide (NO) signaling further amplifies vasodilation. H2S enhances NO bioavailability by inhibiting its degradation and stimulating endothelial nitric oxide synthase (eNOS) activity, increasing cGMP levels and potent vasodilatory responses. Protein sulfhydration, a post-translational modification, plays a crucial role in cell signaling. H2S S-sulfurates oxidized cysteine residues, while polysulfides (H2Sn) are responsible for S-sulfurating reduced cysteine residues. Sulfhydration of key proteins like K_ATP channels and sGC enhances their activity, contributing to the overall vasodilatory effect. Furthermore, H2S interaction with endothelium-derived hyperpolarizing factor (EDHF) pathways adds another layer to its vasodilatory mechanism. By enhancing EDHF activity, H2S facilitates the hyperpolarization and relaxation of VSMCs through gap junctions between endothelial cells and VSMCs. Recent findings suggest that H2S can also modulate transient receptor potential (TRP) channels, particularly TRPV4 channels, in endothelial cells. Activating these channels by H2S promotes calcium entry, stimulating the production of vasodilatory agents like NO and prostacyclin, thereby regulating vascular tone. The comprehensive understanding of H2S-induced vasodilation mechanisms highlights its therapeutic potential. The multifaceted approach of H2S in modulating vascular tone presents a promising strategy for developing novel treatments for hypertension, ischemic conditions, and other vascular disorders. The interaction of H2S with ion channels, cyclic nucleotide signaling, NO pathways, ROS (Reactive Oxygen Species) scavenging, protein sulfhydration, and EDHF underscores its complexity and therapeutic relevance. In conclusion, the intricate signaling paradigms of H2S-induced vasodilation offer valuable insights into its physiological role and therapeutic potential, promising innovative approaches for managing various vascular diseases through the modulation of vascular tone. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a complex, chronic metabolic disease that carries with it a high prevalence of comorbid conditions, making T2DM one of the leading causes of death in the U.S. Traditional lifestyle interventions (e.g., diet, exercise) can counter some adverse effects of T2DM, however, participation in these activities is low with reasons ranging from physical discomfort to lack of time. Thus, there is a critical need to develop novel management strategies that effectively reduce cardiometabolic disease risk and address barriers to adherence. High-resistance inspiratory muscle strength training (IMST) is a time-efficient and simple breathing exercise that significantly reduces systolic and diastolic BP and improves vascular endothelial function in adults with abovenormal blood pressure. Herein we describe the study protocol for a randomized clinical trial to determine the effects of a 6-week IMST regimen on glycemic control and insulin sensitivity in adults with T2DM. Our primary outcome measures include fasting plasma glucose, fasting serum insulin, and insulin resistance utilizing homeostatic model assessment for insulin resistance (HOMA-IR). Secondary outcome measures include resting systolic BP and endothelium-dependent dilation. Further, we will collect plasma for exploratory proteomic analyses. This trial seeks to establish the cardiometabolic effects of 6 weeks of high-resistance IMST in patients with T2DM. [ABSTRACT FROM AUTHOR]

Background: In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium. Methods: A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4–36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates. Results: FMD was inversely correlated with SAF (ρ = -0.50, P < 0.001) and chronological age (ρ = -0.51, P < 0.001). In the multivariable analysis, SAF, chronological age, and male sex were independently associated with reduced FMD (B [95% CI]; -2.60 [-4.40, -0.80]; -0.10 [-0.16, -0.03]; 1.40 [0.14, 2.67], respectively), with the multivariable model adjusted R2 = 0.31, P < 0.001. Conclusions: Higher skin AGE levels, as measured by SAF, were associated with lower FMD values, in a predominantly young, healthy population. Additionally, older age and male participants exhibited significantly lower FMD values, corresponding with compromised endothelial function. These results suggest that SAF, a simple and inexpensive marker, could be used to predict endothelial impairment before the emergence of any structural artery pathophysiology or classic cardiovascular disease risk markers. Trial registration: The study was prospectively registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000821897) and concurrently entered into the WHO International Clinical Trials Registry Platform under the same ID number. [ABSTRACT FROM AUTHOR]

Introduction: Hypercholesterolemia is a risk factor for premature arteriosclerosis. Inflammation and oxidative stress are thought to contribute to endothelial dysfunction preceding vasculopathy. We investigated the association between inflammation, glycocalyx biomarkers, endothelial function, and vascular parameters in children with hypercholesterolemia. Methods: In 22 patients (LDL-cholesterol >130 mg/dL; median age [IQR]: 13 [2.3] years) and 22 controls (13 [2.5] years), tumor necrosis factor-alpha (TNF-α), oxidized cholesterol (oxLDL), and glycocalyx biomarkers (Syndecan-1, Hyaluronan) were measured using immunoassays. Endothelial function was assessed by peripheral arterial tonometry, sublingual glycocalyx and microcirculation by videomicroscopy and carotid intima-media thickness by ultrasound. Results: OxLDL was significantly higher in patients (78.9 [38.2] vs. 50.3 [16.6] U/L, p = 0.002), whereas all other experimental parameters were comparable between groups. Multivariate analysis revealed a significant association of Syndecan-1 with TNF-α (β = 0.75, p < 0.001) and with hypercholesterolemia (β = 0.31, p = 0.030). The interaction term combining TNF-α and hypercholesterolemia showed a significant effect (p = 0.034). Sex was an independent predictor of endothelial function. Conclusion: The combined effect of hypercholesterolemia and inflammation on glycocalyx perturbation and the impact of sex in the premature development of arteriosclerosis deserve further evaluation. Therapeutic approaches tackling low-grade systemic inflammation may offer potential to prevent or delay progression of cardiovascular disease and cardiovascular complications. [ABSTRACT FROM AUTHOR]

Researchers have hypothesized that high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MOD) lead to different patterns of shear stress in the brachial artery. These differing patterns of shear stress are thought to partially explain the differing chronic adaptations to these two types of exercise. No study has directly compared blood flow characteristics during HIIE and MOD. Sixteen healthy males (Age: 23 ± 3 years) completed two randomly assigned exercise visits: HIIE (10 × 1 min intervals at 90–95% of HRmax with 1 min of recovery between) or MOD (30 min at 70% of HRmax) on an electronically braked cycle ergometer. Brachial artery blood flow velocity and diameter were measured for a total of 12 min during each of the exercise sessions. Both anterograde blood flow (MOD: 191.3 ± 80.3 mL/min, HIIE: 153.9 ± 67.5 mL/min, p = 0.03) and shear rate (MOD: 203.5 ± 78.1 s−1, HIIE: 170.8 ± 55.5 s−1, p = 0.04) were higher during MOD compared to HIIE. Both retrograde blood flow (MOD: −48.7 ± 21.3 mL/min, HIIE: −63.9 ± 23.3 cm/s, p < 0.01) and shear rate (MOD: −51.5 ± 19.8 s−1, HIIE: −73.8 ± 28.4 s−1, p < 0.01) were of greater magnitude during HIIE compared to MOD. During exercise, brachial artery diameter (p = 0.34) did not differ between HIIE and MOD. Continuous moderate cycling exercise leads to higher brachial artery anterograde shear rate and blood flow, but lower retrograde shear rate and blood flow when compared to high-intensity interval exercise. These differences during exercise in blood flow characteristics could shed light on the differing chronic adaptations to these two types of exercise. [ABSTRACT FROM AUTHOR]

Vascular aging, marked by alterations in the structure and function of blood vessels, including heightened arterial stiffness and impaired endothelial function, is linked to a higher likelihood of developing cardiovascular and age-associated pathological conditions. Oxidative stress and inflammation are key stimulation factors in vascular aging. Engaging in healthy dietary habits could enhance the functioning of blood vessels. The aim of this study was to conduct a literature review of the evidence regarding the relationship between food regimens, nutraceuticals, and dietary supplements and vascular health. A search of electronic databases, including PubMed, Scopus, and Web of Science Core Collection, was performed. Experimental and observational studies evaluating the association between food groups, nutraceuticals, supplements, and endothelial function and/or arterial stiffness were deemed eligible for this narrative review. Based on the current body of the included studies, food groups, nutraceuticals, and dietary supplements may not demonstrate superiority over placebos in enhancing markers of vascular health. To obtain more reliable evidence on the effectiveness of interventions in vascular health, additional RCTs with larger sample sizes, extended follow-up periods, and multi-center participation are necessary. Enhancing the credibility of these RCTs requires better control of dietary variables and more precise measurement of vascular health markers. [ABSTRACT FROM AUTHOR]

Endothelial function declines with aging and independently predicts future cardiovascular disease (CVD) events. Diving also impairs endothelial function in humans. Yet, dolphins, being long-lived mammals adapted to diving, undergo repetitive cycles of tissue hypoxia-reoxygenation and disturbed shear stress without manifesting any apparent detrimental effects, as CVD is essentially nonexistent in these animals. Thus, dolphins may be a unique model of healthy arterial aging and may provide insights into strategies for clinical medicine. Emerging evidence shows that the circulating milieu (bioactive factors in the blood) is at least partially responsible for transducing reductions in age-related endothelial function. To assess whether dolphins have preserved endothelial function with aging because of a protected circulating milieu, we tested if the serum (pool of the circulating milieu) of bottlenose dolphins (Tursiops truncatus) induces the same arterial aging phenotype as the serum of age-equivalent humans. We incubated conduit arteries from young and old mice with dolphin and human serum and measured endothelial function ex vivo via endothelium-dependent dilation to acetylcholine. Although young arteries incubated with serum from midlife/older adult human serum had lower endothelial function, those incubated with dolphin serum consistently maintained high endothelial function regardless of the age of the donor. Thus, studying the arterial health of dolphins could lead to potential novel therapeutic strategies to improve age-related endothelial dysfunction in humans. NEW & NOTEWORTHY: We demonstrate that, unlike serum of midlife/older adult humans, age-matched dolphin serum elicits higher endothelial function ex vivo in young mouse carotid arteries, suggesting that the circulating milieu of bottlenose dolphins may be geroprotective. We propose that dolphins are a novel model to investigate potential novel therapeutic strategies to mitigate age-related endothelial dysfunction in humans. [ABSTRACT FROM AUTHOR]

Purpose: Postmenopausal women experience augmented aortic hemodynamic responses to isometric handgrip (IHG) exercise and metaboreflex activation post-exercise muscle ischemia (PEMI). Relationships between endothelial function brachial artery flow-mediated dilation (FMD) and aortic stiffness carotid-femoral pulse wave velocity (cfPWV) with aortic pulsatile hemodynamics during IHG and PEMI have not been determined. The relationships between aortic hemodynamic responses to PEMI were evaluated. Methods: Aortic blood pressure (BP), wave reflection, and pressure of forward (Pf) and backward (Pb) waves were measured using arterial tonometry at rest, IHG at 30% maximal force, and PEMI in 30 (15/group) postmenopausal women with low (≤ 4.5%) and normal (≥ 5.5%) FMD. Hemodynamic responses were analyzed as the change (Δ) from rest to the last minute of IHG and PEMI. Results: Brachial and aortic systolic BP (SBP) responses to IHG were higher in the low vs normal FMD group (P < 0.05). Aortic SBP (Δ20 ± 8 vs Δ11 ± 7 mmHg), pulse pressure (PP) (Δ12 ± 8 vs Δ6 ± 4 mmHg), augmented pressure (AP) (Δ5 ± 3 vs Δ2 ± 2 mmHg), and Pb (Δ6 ± 4 vs Δ3 ± 2 mmHg) responses to PEMI were greater (P < 0.05) in women with low vs. normal FMD. FMD was negatively correlated with aortic SBP, PP, AP, and Pb (P < 0.05) responses to PEMI. cfPWV was not correlated with responses to PEMI. Conclusion: Endothelial dysfunction relates to augmented aortic pulsatile load during metaboreflex activation, which may increase cardiovascular risk in postmenopausal women. [ABSTRACT FROM AUTHOR]

Older adults sit during most hours of the day; more than 30% are considered physically inactive. The accumulation of prolonged sitting time is an exercise-independent risk factor for aging-related conditions such as cardiometabolic disease and cancer. Archival plasma samples from a randomized controlled, four-condition crossover study conducted in 10 postmenopausal women with overweight or obesity were analyzed. During 5-hour conditions completed on separate days, the trial tested three interruption modalities: two-minute stands each 20 min (STS), hourly ten-minute standing breaks (Stand), hourly two-minute walks (Walk), and a controlled sit. Fasting baseline and 5-hour end point (2 h postprandial) samples were used for targeted metabolomic profiling. Condition-associated metabolome changes were compared using paired t-tests. STS eliminated the postprandial elevation of amino acid metabolites that was observed in the control. A norvaline derivative shown to have anti-hypertensive and -hyperglycemic effects was significantly increased during Stand and STS. Post-hoc testing identified 19 significantly different metabolites across the interventions. Tight metabolite clustering by condition was driven by amino acid, vasoactive, and sugar metabolites, as demonstrated by partial least squares-discriminant analyses. This exploratory study suggests that brief, low-intensity modalities of interrupting prolonged sitting can acutely elucidate beneficial cardiometabolic changes in postmenopausal women with cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Abstract Background Night shift workers face increased risk of cardiovascular disease (CVD) compared to non-shift workers. Evidence supports on-shift napping and regular non-invasive monitoring of endothelial function for risk mitigation, yet neither strategy is widely used. Methods We evaluated the feasibility of non-invasive assessment of peripheral arterial tone (PAT) to assess the effect of napping during simulated night shift work on endothelial function. We used a single-site, randomized crossover trial of simulated night shift work with a 45-min nap condition versus a control, no-nap condition (ClinicalTrials.gov NCT05436951). Results The primary outcome was the number of participants with ≥ 70% of endothelial function assessments. Secondary outcomes included mean reactive hyperemia index (RHI), BP, and cognitive performance with the brief psychomotor vigilance task (PVT-B). Of the 10 consented, 9 completed both conditions. All participants exceeded feasibility benchmarks. Mean RHI did not differ by nap condition, and the delta from pre- to post measure did not differ (difference in delta = − 0.26, 95% CI − 1.09, 0.58). Hourly PVT-B assessments from 19:00 to 07:00 h did not differ by nap condition. Compared to pre-nap measures, cognitive performance on the PVT-B was poorest at + 0 min post-nap. Conclusion Our findings can inform larger studies evaluating the effects of night shift work and napping on endothelial function. Trial registrations ClinicalTrials.gov (NCT05436951, registered on June 23, 2022).

Background: The escalating global burden of cardiovascular diseases, largely driven by unhealthy lifestyle choices and dietary patterns, has intensified the search for effective and safe interventions. With current treatments often marred by significant side effects, the exploration of natural compounds such as flavonoids presents a compelling alternative. Objective: This study investigated the effects of fermented citrus bioconversion product (FCBP), a fermented citrus bioflavonoid, on various markers of cardiovascular health in the context of a high-fat diet. Design: In vivo, a high-fat diet-induced mouse model was used to assess the effects of FCBP on body weight, serum nitric oxide (NO) levels, activated partial thromboplastin time (aPTT), phosphatidylserine (PS) exposure on red blood cells, and the expression of inflammatory markers Intercellular Adhesion Molecule (ICAM)-1 and Vascular Cell Adhesion Molecule (VCAM)-1 in the thoracic aorta. In vitro, EA.hy926 endothelial cells were used to evaluate the compound’s effects on cell viability, NO production, endothelial nitric oxide synthase (eNOS) expression, and cell adhesion molecule (CAM) levels to further understand the mechanisms behind the in vivo findings. Results: In vivo, FCBP supplementation led to a dose-dependent reduction in weight gain, a significant decrease in serum NO levels at 10 mg/kg, and reduced ICAM-1 and VCAM-1 expressions in the thoracic aorta, indicating anti-inflammatory properties. PS exposure on red blood cells was also reduced, suggesting decreased procoagulant activity, while aPTT remained unchanged. In vitro, FCBP was non-cytotoxic to endothelial cells, showed a trend toward increased NO production and eNOS expression, and reduced the expression of ICAM-1 and VCAM-1, supporting its potential anti-inflammatory effects. Conclusions: FCBP demonstrates potential as a bioactive compound for managing cardiovascular health by reducing inflammation, mitigating weight gain, and influencing blood circulation-related parameters under high-fat diet conditions. Further studies, including diverse models and human trials, are warranted to elucidate its mechanisms and compare its efficacy with established cardiovascular therapeutics.

Objective: Gestational diabetes mellitus (GDM) and preeclampsia are the most common medical complications of pregnancy. Both GDM and preeclampsia are risk factors for cardiovascular diseases (CVD) and atherosclerosis. Flow-mediated dilatation (FMD) is a good ultrasonographic marker of early atherosclerotic changes used to measure endothelial function. In this study; we evaluated FMD, an indicator of endothelial function, and investigated whether there was an increased risk of CVD in patients with a history of preeclampsia or GDM. Methods: The study was carried out with 104 patients who gave birth in the Obstetrics and Gynecology Clinic of Bolu Abant İzzet Baysal University Training and Research Hospital between January 2016 and January 2017. Thirty four patients with a history of preeclampsia, 37 patients with a history of GDM, and 33 patients with uncomplicated deliveries were included in the study. All patients in the study had only one live birth and their age range was between 20 and 30 years. Demographic data, cardiovascular risk markers, obstetric data, laboratory tests and FMD change (%) measurements of all patients were compared. Mean and standard deviation values of the obtained data were calculated. Results: The mean FMD change (%) in the group of patients with a history of preeclampsia was 9.8±3.1. It was 10.32±2.50 in the group of patients with a history of GDM and it was 13.19±3.03 in the control group. A statistically significant difference was found between the control group and GDM and preeclampsia groups in terms of FMD change (%) (

Abstract Introduction Endothelial dysfunction (ED) promotes the development of atherosclerosis, and studies suggest an association with age-related neurocognitive disorders. It is currently unclear whether ED is also associated with the risk of perioperative neurocognitive disorders. Method We included 788 participants aged ≥ 65 years of the BioCog study. Patients were scheduled to undergo elective surgery with expected duration > 60 min. Blood was collected before surgery for measurement of 5 biomarkers of ED: asymmetric and symmetric dimethylarginine (ADMA; SDMA), intercellular and vascular adhesion molecule (ICAM-1, VCAM-1), and von Willebrand factor (vWF). Patients were monitored for the occurrence of postoperative delirium (POD) daily until the 7th postoperative day. 537 (68.1%) patients returned for a 3-month follow-up. Post-operative cognitive dysfunction (POCD) was defined from the change in results on a battery of 6 neuropsychological tests between baseline and 3 months, compared to the change in results of a control group during the 3-month interval. The associations of each of the 5 ED biomarkers with POD and POCD respectively were determined using multiple logistic regression analyses with adjustment for age, sex, surgery type, pre-morbid IQ, body mass index, hypertension, diabetes, HbA1C, triglyceride, total and HDL cholesterol. Results 19.8% of 788 patients developed POD; 10.1% of 537 patients had POCD at 3 months. Concentrations of ED biomarkers were not significantly associated with a POD. A higher VCAM-1 concentration was associated with a reduced POCD risk (adjusted odds ratio 0.55; 95% CI: 0.35–0.86). No further statistically significant results were found. Conclusion Pre-operative concentrations of ED biomarkers were not associated with POD risk. We unexpectedly found higher VCAM-1 to be associated with a reduced POCD risk. Further studies are needed to evaluate these findings.

Physical activity (PA) has beneficial effects on erectile dysfunction (ED). It has been proposed to affect ED physiologically via the vascular and nervous systems. This study aimed to evaluate the effect of physical activity on endothelial erectile function, sex hormones and sperm production in healthy males. Sixty-one healthy men aged 18–35 years were eligible to participate in this biochemical and questionnaire-based study. The participants were classified into two groups according to their physical activity level: a physically active group (PA = 38) and a physically inactive group (PINA = 23). PA was evaluated using the ACTi graph GT1M accelerometer. Erectile function was evaluated using the International Index of Erectile Function (IIEF-15) questionnaire. The levels of the sex hormones testosterone (T) and free testosterone (f-T), and the nitric oxide (NO) and E-selectin levels were measured by enzyme linked immuno sorbent assay (ELISA). In addition, a complete semen analysis was performed for all subjects. Better sperm production was reported in physically active subjects than in nonactive subjects. There was a significant increase (p = 0.001) in the IIEF-15 score, and the levels of T, f-T, NO and E-selectin were estimated in physically active subjects compared with those in nonactive subjects. Erectile function (IIEF-15 score) correlated positively with PA and with increased levels of T, f-T, NO and E-selectin, whereas the IIEF-15 score correlated negatively with age and adiposity. Seminological parameters such as the spermatozoa concentration, sperm viability, motility, morphology and normal forms were significantly improved in physically active subjects. Physical activity at mild to moderate levels is significantly associated with improved erectile function, increased endothelial function, increased sex hormone levels and better sperm production in healthy men aged 18–35 years. This study proposes that physical activity physiologically affects erectile function and spermatogenesis via cellular free radical-antioxidant mechanisms.

Abstract Background In populations with chronic disease, skin autofluorescence (SAF), a measure of long-term fluorescent advanced glycation end-products (AGEs) accumulation in body tissues, has been associated with vascular endothelial function, measured using flow-mediated dilation (FMD). The primary aim of this study was to quantify the relationship between endothelial function and tissue accumulation of AGEs in adults from the general population to determine whether SAF could be used as a marker to predict early impairment of the endothelium. Methods A cross-sectional study was conducted with 125 participants (median age: 28.5 y, IQR: 24.4–36.0; 54% women). Endothelial function was measured by fasting FMD. Skin AGEs were measured as SAF using an AGE Reader. Participant anthropometry, blood pressure, and blood biomarkers were also measured. Associations were evaluated using multivariable regression analysis and were adjusted for significant covariates. Results FMD was inversely correlated with SAF (ρ = -0.50, P

Abstract 30 min of moderate-intensity aerobic exercise per day is recommended, but the response and adaptation of endothelial function (EF) to this exercise remains controversial. The purpose of this study was to determine the changes in EF in endurance trained and untrained individuals before and after this exercise and to compare the differences between trained and untrained individuals. Twelve endurance-trained male college athletes (trained group) and 12 untrained male college students (untrained group) performed a 30-min run at an intensity of 60% VO2max. Brachial artery flow-mediated dilation (FMD) was measured before exercise, 30 min and 60 min after exercise, and the following morning. Resting diameter and maximum diameter showed large time effects (p

Purpose: To summarize the evidence on associations of adiposity and cardiorespiratory fitness (CRF) with arterial structure and function in nonclinical children and adolescents. Methods: Two researchers conducted a search in 5 electronic databases in April 2022 to find studies in nonclinical youth (age 5–17.9 y) reporting multivariable associations. Studies were eligible if adiposity and/or CRF were used as the predictor and arterial structure and/or function was the outcome. The Quality Assessment Tool for Quantitative Studies was used to assess methodological quality for experimental studies, and a modified version was used for observational studies. Results: Ninety-nine studies (72.7% cross-sectional) were included. Ninety-four assessed associations between adiposity and arterial outcomes, most using overall body proportion (n = 71), abdominal (n = 52), or whole-body adiposity (n = 40). Most evidence was inconsistent or nonsignificant, but 59 studies suggested higher abdominal adiposity and worse body proportion were associated with adverse arterial outcomes. Twenty-one assessed associations between CRF and arterial outcomes, with findings inconsistent. Most evidence was rated weak in quality. Conclusion: While high adiposity may contribute to poor arterial outcomes, evidence is limited regarding CRF. Future studies should disentangle these associations by studying youth with healthy adiposity but poor CRF, or vice versa, using longitudinal or experimental study designs. [ABSTRACT FROM AUTHOR]

Rho-kinase has been implicated in the development of hypertension in preclinical studies and may contribute to age-related blood pressure elevation. This study tested the hypothesis that Rho-kinase contributes to elevated systolic blood pressure (SBP) in healthy older adults. Young (18–30 years, 6F/6M) and older (60–80 years, 7F/6M) adults were enrolled in a double-blind, placebo-controlled crossover study using intravenous fasudil infusion to inhibit Rho-kinase. Fasudil lowered SBP in older adults compared to placebo (saline) (2-h post-infusion: 125 ± 4 vs. 133 ± 4 mmHg, P < 0.05), whereas fasudil had no impact on SBP in young adults. Immediately following fasudil infusion, there was a transient reduction in mean arterial pressure (MAP) in young adults that was no longer evident 1-h post-infusion. In older adults, MAP remained lower throughout the fasudil visit compared to placebo (2-h post-infusion: 93 ± 3 vs. 100 ± 3 mmHg, P < 0.05) such that age-related differences in SBP and MAP were abolished. Aortic stiffness (carotid-femoral pulse wave velocity) was not altered by fasudil when central MAP was included as a covariate in analyses. Fasudil reduced forearm vascular resistance in older (2-h post-infusion: 3.3 ± 0.4 vs. 4.8 ± 0.6 mmHg/ml/min, P < 0.05) but not young (4.0 ± 0.6 vs. 3.8 ± 0.5 mmHg/ml/min) adults, which was accompanied by an increase in brachial artery diameter only in older adults. Brachial artery flow-mediated dilation was not affected by fasudil in either group. These findings indicate that Rho-kinase inhibition reduces SBP in healthy older but not young adults, which is associated with a concomitant reduction in forearm vascular resistance. [ABSTRACT FROM AUTHOR]

Abstract Background Performing reproducible flow-mediated dilatation (FMD) measurements can be challenging, especially among inexperienced operators. Our aim was to present the detailed learning curve of a novice operator. Methods Following a one-week basic training period, the operator performed duplicate measurements on 6–8 individuals per week, for six weeks. The operator followed the recommendations of the most recent guideline. Duplex ultrasound was used for the simultaneous and continuous measurement of brachial artery diameter and local blood flow velocity. Following a 1-min recording of baseline diameter (D), FMD was measured after a 5-min period of occlusion of the proximal forearm vessels. Inter-session coefficient of variation (CV) values for D and FMD were calculated for each week. Results The number of volunteers assessed each week were the following: 8, 7, 7, 6, 7, 7 individuals. CV values for both D and FMD exhibited a decreasing trend over the training period, ending at 1.73% for D and 14.24% for FMD at week 6. These CV values are within the range outlined in the most recent FMD guideline for proficiency. Conclusion Within a reasonable timeframe, and with careful adherence to measurement guidelines, the attainment of sound reproducibility in FMD measurements by a novice operator is feasible.

Abstract Background In assessing the effects of smoking cessation on endothelial function, low-flow-mediated constriction (L-FMC) may provide complementary information to flow-mediated dilation (FMD). However, the value of flow-mediated total dilation (FMTD), an index that incorporates L-FMC into FMD, remains underreported. We aimed to evaluate the effect of smoking cessation on endothelial function, as assessed by FMD and FMTD, and clarify its associated clinical factors. Methods We enrolled 118 consecutive current smokers without previous coronary artery disease (72.9% were men; age: 59 ± 11 years) who underwent smoking cessation treatment. The clinical variables %FMD, %L-FMC, and %FMTD were examined before and 20 weeks after treatment initiation. A multivariate linear regression model was used to investigate the effects of smoking cessation on %FMD and %FMTD and the interaction between smoking cessation and baseline clinical variables. Results After 20 weeks, 85 smokers (69.4% were men; age: 59 ± 12 years) ceased smoking (abstainers), whereas 33 smokers (81.8% were men; age: 58 ± 11 years) did not (continued smokers). The estimated group differences (abstainers - continued smokers) in changes in the %FMD and %FMTD were 0.77% (95% confidence interval [CI], -0.22–1.77%; p = 0.129) and 1.17% (95% CI, 0.16–2.18%; p = 0.024), respectively. Smoking cessation-associated improvement in %FMTD was greater in women than in men (5.41% [95% CI, 3.15–7.67%] versus 0.24% [95% CI, -0.81–1.28%]; p-value for interaction,

Abstract This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave‐reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points—Baseline (BL), following 10, 20, 30 and 40 km, 1 h post‐completion (1HP) and 24 h post‐completion (24HP). Flow‐mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P

Researchers have hypothesized that high-intensity interval exercise (HIIE) and moderate-intensity continuous exercise (MOD) lead to different patterns of shear stress in the brachial artery. These differing patterns of shear stress are thought to partially explain the differing chronic adaptations to these two types of exercise. No study has directly compared blood flow characteristics during HIIE and MOD. Sixteen healthy males (Age: 23 ± 3 years) completed two randomly assigned exercise visits: HIIE (10 × 1 min intervals at 90–95% of HRmax with 1 min of recovery between) or MOD (30 min at 70% of HRmax) on an electronically braked cycle ergometer. Brachial artery blood flow velocity and diameter were measured for a total of 12 min during each of the exercise sessions. Both anterograde blood flow (MOD: 191.3 ± 80.3 mL/min, HIIE: 153.9 ± 67.5 mL/min, p = 0.03) and shear rate (MOD: 203.5 ± 78.1 s−1, HIIE: 170.8 ± 55.5 s−1, p = 0.04) were higher during MOD compared to HIIE. Both retrograde blood flow (MOD: −48.7 ± 21.3 mL/min, HIIE: −63.9 ± 23.3 cm/s, p < 0.01) and shear rate (MOD: −51.5 ± 19.8 s−1, HIIE: −73.8 ± 28.4 s−1, p < 0.01) were of greater magnitude during HIIE compared to MOD. During exercise, brachial artery diameter (p = 0.34) did not differ between HIIE and MOD. Continuous moderate cycling exercise leads to higher brachial artery anterograde shear rate and blood flow, but lower retrograde shear rate and blood flow when compared to high-intensity interval exercise. These differences during exercise in blood flow characteristics could shed light on the differing chronic adaptations to these two types of exercise.

Background: Evidence has demonstrated that non-habitual exercise, such as eccentric exercise, can increase reactive oxygen species and induce endothelial dysfunction, which plays a central role in the development of cardiovascular disease. Polyphenol-rich foods, such as cocoa, have been widely investigated in vascular function due to their antioxidant effect. Aims: The goal of this study was to evaluate the impact of microencapsulated cocoa (MC) polyphenols in the flow-mediated dilation (FMD) response and forearm muscle oxygenation (StO2) parameters after an eccentric exercise. Methods: Thirteen physically active adults were enrolled in a randomized, double-blind, and crossover study. FMD and StO2 were evaluated before and after 24 h, 48 h, and 72 h of eccentric exercise and MC or placebo supplementation. Results: No significant difference in FMD response and StO2 parameters was observed after MC and placebo (p > 0.05). Conclusions: A single dose of MC did not change FMD and muscle StO2 parameters after eccentric exercise in healthy individuals.

Abstract Background The COVID-19 has been shown to have negative effects on the cardiovascular system, but it is unclear how long these effects last in college students. This study aimed to assess the long-term impact of COVID-19 on arterial stiffness, endothelial function, and blood pressure in college students. Methods We enrolled 37 college students who had been infected with COVID-19 for more than 2 months. Brachial artery flow-mediated dilation (FMD) was used to assess endothelial function, while arterial stiffness was evaluated using the ABI Systems 100, including variables such as ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), carotid-femoral pulse wave velocity (cfPWV), heart rate (HR), and blood pressure (BP). Results Our results showed that FMD was significantly impaired after COVID-19 infection (p 0.05). Conclusion: Our study demonstrated that COVID-19 has long-term detrimental effects on vascular function in college students. However, arterial stiffness tends to improve over time, while BP may exhibit the opposite trend.

Abstract Background This study aims to analyze the efficacy of metformin on carotid intima media thickness (CIMT) and flow-mediated dilation (FMD) for patients with polycystic ovary syndrome (PCOS). Methods A literature search of PubMed, Embase, and the Cochrane Library from inception to December 2023 was conducted. Then, after studies selection and data extraction, the mean difference (MD) with a 95% confidence interval (CI) was used to evaluate metformin efficacy in CIMT and FMD for PCOS patients. Heterogeneity was investigated through subgroup and sensitivity analysis. The protocol of our study has been registered in PROSPERO (CRD42024497239). Results A total of 12 studies with 248 patients were included. CIMT was lower in the endpoint group (after metformin) compared with the baseline group (before metformin) (MD = -0.11, 95% CI = -0.21 to -0.01, p = 0.04). FMD was higher in the endpoint group compared with the baseline group (MD = 3.25, 95% CI = 1.85 to 4.66, p

Abstract Endothelial dysfunction is acknowledged as a marker for subclinical target organ damage (STOD) in hypertension, though its therapeutic potential has not yet been clarified. This study assessed whether early endothelial function improvement (EEFI) reduced STOD in patients with essential hypertension (EH). We conducted a retrospective cohort analysis of 456 EH patients initially free from STOD. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD), with values ≤ 7.1% indicating dysfunction. Patients were initially categorized by endothelial status (dysfunction: n = 180, normal: n = 276), and further divided into improved or unimproved groups based on changes within three months post-enrollment. During a median follow-up of 25 months, 177 patients developed STOD. The incidence of STOD was significantly higher in patients with initial dysfunction compared to those with normal function. Kaplan–Meier analysis indicated that the improved group had a lower cumulative incidence of STOD compared to the unimproved group (p