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Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin-like modifier (SUMO)-mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated. It is discovered that TEAD1 is modified by SUMO1 during cardiac hypertrophy and that the process of deSUMOylation is regulated by SUMO-specific protease 1 (SENP1). Lysine 173 is an essential site for TEAD1 SUMOylation, which affects the protein stability, nuclear localization, and DNA-binding ability of TEAD1 and enhances the interaction between TEAD1 and its transcriptional co-activator yes-associated protein 1 in the Hippo pathway. Finally, adeno-associated virus serotype 9 is used to construct TEAD1 wild-type and KR mutant mice and demonstrated that the deSUMOylation of TEAD1 markedly exacerbated cardiomyocyte enlargement in vitro and in a mouse model of cardiac hypertrophy. The results provide novel evidence that the SUMOylation of TEAD1 is a promising therapeutic strategy for hypertrophy-related heart failure., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Background: Left bundle branch area pacing (LBBAP) includes left bundle branch pacing (LBBP) and left ventricular (LV) septal myocardial pacing (LVSP)., Hypothesis: The study aimed to assess resynchronization effects and clinical outcomes by LBBAP in heart failure (HF) patients with cardiac resynchronization therapy (CRT) indications., Methods: LBBAP was successfully performed in 29 consecutive patients and further classified as the LBBP-group (N = 15) and LVSP-group (N = 14) based on the LBBP criteria and novel LV conduction time measurement (LV CT, between LBBAP site and LV pacing (LVP) site). AV-interval optimized LBBP or LVSP, or LVSP combined with LVP (LVSP-LVP) was applied. LV electrical and mechanical synchrony and clinical outcomes were assessed., Results: All 15 patients in the LBBP-group received optimized LBBP while 14 patients in the LVSP-group received either optimized LVSP (5) or LVSP-LVP (9). The LV CT during LBBP was significantly faster than that during LVP (p < .001), while LV CT during LVSP were similar to LVP (p = .226). The stimulus to peak LV activation time (Stim-LVAT, 71.2 ± 8.3 ms) and LV mechanical synchrony (TSI-SD, 35.3 ± 9.5 ms) during LBBP were significantly shorter than those during LVSP (Stim-LVAT 89.1 ± 19.5 ms, TSI-SD 49.8 ± 14.4 ms, both p < .05). Following 17(IQR 8) months of follow-up, the improvement of LVEF (26.0%(IQR 16.0)) in the LBBP-group was significantly greater than that in the LVSP-group (6.0%(IQR 20.8), p = .001)., Conclusions: LV activation in LBBP propagated significantly faster than that of LVSP. LBBP generated superior electrical and mechanical resynchronization and better LVEF improvement over LVSP in HF patients with CRT indications., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)

Objective: Pulmonary arterial hypertension (PAH) is a chronic progressive disease that may lead to right heart failure (RHF) and early death. Balloon atrial septostomy (BAS) may be used for the palliative treatment of RHF from PAH. We present our contemporary institutional experience of utilizing BAS in idiopathic PAH (IPAH) patients with refractory RHF to investigate the effect on the safety, efficacy and long-term survival., Methods: This retrospective analysis included 12 IPAH patients with severe RHF from March 2017 to May 2019 who were assessed as high risk. All patients received standard treatment including combination of PAH-specific drugs. Graded BAS was performed on these patients due to unsatisfactory clinical response. Clinical, functional and hemodynamic variables before and immediately after the procedure were collected. 1-year follow-up outcomes and 3-year survival rate were further analyzed., Results: Successful septostomy was achieved in cases with no procedure-related complications. All patients obtained hemodynamic improvement immediately after the procedure. The WHO functional class and exercise endurance improved at 1-year follow-up, 7 of 12 patients achieved intermediate-low risk status, while the rest remained at intermediate-high risk. 2 patients died at 18 and 20 months due to malignant arrhythmia and advanced heart failure, respectively. Survival at 1 year and 3 years was 100% and 83.3%., Conclusions: In selected IPAH patients with refractory RHF, BAS is an additional therapeutic strategy, especially when PAH-specific drugs could not achieve the treatment target. BAS can improve hemodynamic variables, bring clinical and cardiac functional benefits and increase the 3-year survival., Competing Interests: Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Exercise training protects the heart against pathological cardiac remodeling and confers cardioprotection from heart failure. However, the underlying mechanism is still elusive., Methods: An integrative analysis of multi-omics data of the skeletal muscle in response to exercise is performed to search for potential exerkine. Then, CCDC80tide is examined in humans after acute exercise. The role of CCDC80tide is assessed in a mouse model of hypertensive cardiac remodeling and in hypertension-mediated cell injury models. The transcriptomic analysis and immunoprecipitation assay are conducted to explore the mechanism., Findings: The coiled-coil domain-containing protein 80 (CCDC80) is found strongly positively associated with exercise. Interestingly, exercise stimuli induce the secretion of C-terminal CCDC80 (referred as CCDC80tide hereafter) via EVs-encapsulated CCDC80tide into the circulation. Importantly, cardiac-specific expression of CCDC80tide protects against angiotensin II (Ang II)-induced cardiac hypertrophy and fibrosis in mice. In in vitro studies, the expression of CCDC80tide reduces Ang II-induced cardiomyocyte hypertrophy, cardiac microvascular endothelial cell (CMEC) inflammation, and mitigated vascular smooth muscle cell (VSMC) proliferation and collagen formation. To understand the cardioprotective effect of CCDC80tide, a transcriptomic analysis reveals a dramatic inhibition of the STAT3 (Signal transducer and activator of transcription 3) signaling pathway in CCDC80tide overexpressing cells. Mechanistically, CCDC80tide selectively interacts with the kinase-active form of JAK2 (Janus kinase 2) and consequently inhibits its kinase activity to phosphorylate and activate STAT3., Interpretation: The results provide new insights into exercise-afforded cardioprotection in pathological cardiac remodeling and highlight the therapeutic potential of CCDC80tide in heart failure treatment., Funding: This work was supported by the National Natural Science Foundation of China [Grant/Award Numbers: 81770428, 81830010, 82130012, 81900438, 82100447); Shanghai Science and Technology Committee [Grant/Award Numbers: 21S11903000, 19JC1415702]; Emerging and Advanced Technology Programs of Hospital Development Center of Shanghai [Grant/Award Number: SHDC12018129]; China Postdoctoral Science Foundation [2021M692108]; and China National Postdoctoral Program for Innovative Talents [BX20200211]., Competing Interests: Declaration of interests None declared., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Right ventricular (RV) dysfunction is known to be highly correlated with mortality and morbidity; nevertheless, imaging-based assessment of RV anatomy and physiology lags far behind that of the left ventricle. In this study, we advance RV imaging using cardiac magnetic resonance (CMR) to accomplish the following aims: (i) track the motion of six tricuspid annular (TA) sites using a semi-automatic tracking system; (ii) extract clinically important TA measurements-systolic velocity (Sm), early diastolic velocity (Em), late diastolic velocity (Am), and TA plane systolic excursion (TAPSE)-for each TA site and compare these CMR-derived measurements in healthy subjects vs. patients with heart failure, repaired tetralogy of Fallot, pulmonary hypertension, and hypertrophic cardiomyopathy; (iii) investigate how the TA motion related measurements compare with information provided by invasive right heart catheterization (RHC); (iv) evaluate the rate of change in surface area swept out by the reconstructed tricuspid annulus over time and (v) assess the reproducibility of this CMR-based technique. Results indicate that TA motion parameter data obtained in three dimensions using the proposed CMR-based systematic methodology achieve superior diagnostic performance (Sm: AUC = 0.957; TAPSE: AUC = 0.981) compared to two-dimensional CMR imaging. Both Sm and TAPSE from CMR correlated positively with dP/dt max /IP from RHC (Sm: r = 0.621, p < 0.01; TAPSE: r = 0.648, p < 0.01). Our highly reproducible and robust methodology holds potential for extending CMR imaging to characterization of TA morphology and dynamic behaviour, eventually leading to deeper understanding of RV function and improved diagnostic capability.

Ubiquitin-specific protease 18 (USP18), a USP family member, is involved in antiviral activity and cancer inhibition. Although USP18 is expressed in heart, the role of USP18 in the heart and in cardiac diseases remains unknown. Here, we show that USP18 expression is elevated in both human dilated hearts and hypertrophic murine models. Cardiomyocyte-specific overexpression of USP18 in mice significantly blunted cardiac remodeling as evidenced by mitigated myocardial hypertrophy, fibrosis, ventricular dilation, and preserved ejection function, whereas USP18-deficient mice displayed exacerbated cardiac remodeling under the same pathological stimuli. Similar results were observed for in vitro angiotensin II-induced neonatal rat cardiomyocyte hypertrophy. The antihypertrophic effects of USP18 under hypertrophic stimuli were associated with the blockage of the transforming growth factor-β-activated kinase 1-p38/c-Jun N-terminal kinase 1/2 signaling cascade. Blocking transforming growth factor-β-activated kinase 1-p38/c-Jun N-terminal kinase 1/2 signaling with a pharmacological inhibitor (5Z-7-oxozeaenol) greatly reversed the detrimental effects observed in USP18-knockout mice subjected to aortic banding. Our data indicate that USP18 inhibits cardiac hypertrophy and postpones cardiac dysfunction during the remodeling process, which is dependent on its modulation of the transforming growth factor-β-activated kinase 1-p38/c-Jun N-terminal kinase 1/2 signaling axis. Thus, USP18 is a potent therapeutic target for heart failure treatment., (© 2016 American Heart Association, Inc.)

Vagus nerve stimulation (VNS), targeting the imbalanced autonomic nervous system, is a promising therapeutic approach for chronic heart failure (HF). Moreover, calcium cycling is an important part of cardiac excitation-contraction coupling (ECC), which also participates in the antiarrhythmic effects of VNS. We hypothesized that low-level VNS (LL-VNS) could improve cardiac function by regulation of intracellular calcium handling properties. The experimental HF model was established by ligation of the left anterior descending coronary artery (LAD). Thirty-two male Sprague-Dawley rats were divided into 3 groups as follows; control group (sham operated without coronary ligation, n = 10), HF-VNS group (HF rats with VNS, n = 12), and HF-SS group (HF rats with sham nerve stimulation, n = 10). After 8 weeks of treatment, LL-VNS significantly improved left ventricular ejection fraction (LVEF) and attenuated myocardial interstitial fibrosis in the HF-VNS group compared with the HF-SS group. Elevated plasma norepinephrine and dopamine, but not epinephrine, were partially reduced by LL-VNS. Additionally, LL-VNS restored the protein and mRNA levels of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a), Na(+)-Ca(2+) exchanger 1 (NCX1), and phospholamban (PLB) whereas the expression of ryanodine receptor 2 (RyR2) as well as mRNA level was unaffected. Thus, our study results suggest that the improvement of cardiac performance by LL-VNS is accompanied by the reversal of dysfunctional calcium handling properties including SERCA2a, NCX1, and PLB which may be a potential molecular mechanism of VNS for HF.

Instruction and Objectives . Noninvasive positive pressure ventilation (NPPV) alleviates sleep-disordered breathing (SDB) and it may improve cardiac function in SDB patients. Because large randomized controlled trials directly evaluating the impact of NPPV on cardiac function are lacking, we conducted a meta-analysis of published data on effectiveness of NPPV in improving cardiac function in patients with chronic heart failure regardless of SDB presence. Methods . Controlled trials were identified in PubMed, OVID, and EMBASE databases. Both fixed and randomized models were used in meta-analysis with primary outcomes of left ventricular ejection fraction (LVEF). Results . Nineteen studies were included with a total of 843 patients. Compared to standard medical treatment (SMT) plus sham-NPPV or SMT only, NPPV plus SMT was associated with improvement in LVEF (weighted mean difference 5.34, 95% CI, [3.85,6.82]; P < 0.00001) and plasma brain natriuretic peptide (BNP) level (weighted mean difference -117.37, 95% CI, [-227.22, -7.52]; P = 0.04) and no influence on overall mortality (RR 1.00, 95% CI, [0.96,1.04]; P = 0.95). Conclusions . In the present meta-analysis, use of NPPV plus SMT improved LVEF and reduced plasma BNP level but did not improve overall mortality in patients with chronic heart failure., Competing Interests: The authors have no financial disclosures or competing interests to declare.

Background: Sympathetic activation and parasympathetic withdrawal are important characteristics of heart failure. Recent studies demonstrate that galanin reduces the discharge of acetylcholine and inhibits vagal bradycardia by acting on galanin receptor type 1 (GalR1). We speculated that blocking GalR1 is beneficial for heart failure., Methods: Rats with heart failure were induced by myocardial infarction. The rats were injected intraperitoneally with galanin receptor antagonist M40 solution (30 nmol/kg) or saline for 4 weeks. Cardiac function was assessed by echocardiography and brain natriuretic peptide (BNP) in plasma. The ratio of heart weight to body weight (HW/BW), hematoxylin-eosin (HE), and Masson trichrome stain was used to evaluate cardiac remodeling. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) in plasma, and sarco(endo)plasmic reticulum Ca(2+) -ATPase (SERCA2) in heart tissue were detected to confirm the mechanism of the cardioprotection effect., Results: Compared with rats injected with saline, M40 effectively improved cardiac function of contraction; decreased BNP, IL-6, and HW/BW (all P < 0.05); attenuated cardiac fibrosis; and upregulated SERCA2 (P < 0.05)., Conclusion: M40 improves cardiac function and attenuates remodeling, suggesting that galanin receptor antagonist may be a potential therapeutic agent for HF., (© 2015 John Wiley & Sons Ltd.)

Background: Heart failure (HF) is a debilitating condition that affects millions of people worldwide. One means of treating HF is cardiac resynchronization therapy (CRT). Recently, several studies have examined the use of echocardiography (ECHO) in the optimization of left ventricular (LV) lead placement to increase the response to CRT. The objective of this study was to synthesize the available data on the comparative efficacy of image-guided and standard CRT., Methods: We searched the PubMed, Cochrane, Embase, and ISI Web of Knowledge databases through April 2014 with the following combinations of search terms: left ventricular lead placement, cardiac resynchronization therapy, image-guided, and echocardiography-guided. Studies meeting all of the inclusion criteria and none of the exclusion criteria were eligible for inclusion. The primary outcome measures were CRT response rate, change in LV ejection fraction (LVEF), and change in LV end systolic volume (LVESV). Secondary outcomes included the rates of all-cause mortality and HF-related hospitalization., Results: Our search identified 103 articles, 3 of which were included in the analysis. In total, 270 patients were randomized to the image-guided CRT and 241, to the standard CRT. The pooled estimates showed a significant benefit for image-guided CRT (CRT response: OR, 2.098, 95 % CI, 1.432-3.072; LVEF: difference in means, 3.457, 95 % CI, 1.910-5.005; LVESV: difference in means, -20.36, 95 % CI, -27.819 - -12.902)., Conclusions: Image-guided CRT produced significantly better clinical outcomes than the standard CRT. Additional trials are warranted to validate the use of imaging in the prospective optimization of CRT.

Background: The aim of this study was to establish a score system derived from clinical, echocardiographic and electrocardiographic indexes and evaluate its clinical value for cardiac resynchronization therapy (CRT) patient selection., Methods: Ninety-three patients receiving CRT were enrolled. A patient selection score system was generated by the clinical, echocardiographic and electrocardiographic parameters achieving a significant level by univariate and multivariate Cox regression model. The positive response to CRT was a left ventricular end systolic volume decrease of ≥ 15% and not reaching primary clinical endpoint (death or re-hospitalization for heart failure) at the end of follow-up., Results: Thirty-nine patients were CRT non-responders (41.94%) and 54 were responders (58.06%). A 4-point score system was generated based on tricuspid annular plane systolic excursion (TAPSE), longitudinal strain (LS), and complete left bundle branch block (CLBBB) combined with a wide QRS duration (QRSd). The sensitivity and specificity for prediction of a positive response to CRT at a score > 2 were 0.823 and 0.850, respectively (AUC: 0.92295% CI 0.691-0.916, p< 0.001)., Conclusions: A patient selection score system based on the integration of TAPSE, LS and CLBBB combined with a wide QRSd can help to predict positive response to CRT effectively and reliably.

Background: Although left ventricular pacing (LVP) leads to a greater acute hemodynamic response than does biventricular pacing (BVP), the long-term effects are diverse. We aimed to assess the efficacy of LVP and BVP in patients undergoing cardiac resynchronization therapy and determine which patients would benefit more from LVP or BVP., Methods: Randomized controlled trials that compared left and biventricular pacing were retrieved from MEDLINE and analyzed for changes in cardiac function and dimensions, cardiac resynchronization therapy response, and electromechanical effects., Results: A total of 811 patients were included from 9 trials. After a mean follow-up, a shorter QRS duration (-40.92 milliseconds; 95% confidence interval [CI], -64.50 to -17.34; P = 0.0007), and improved left ventricular dimensions were observed in the BVP group compared with the LVP group. Moreover, the BVP group had a longer 6-minute hall walk (6MHW) test (37.19 m; 95% CI, 4.72 to 69.67; P = 0.02)., Conclusion: Our results indicate that BVP results in a better electromechanical effect and leads to a better 6MHW test. For all other test criteria, LVP showed a benefit equal to that of BVP. Thus, there is currently insufficient evidence to advocate for LV-only pacing., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Few studies have directly compared cardiac resynchronisation therapy (CRT) with combined CRT-cardioverter defibrillator therapy (CRT-D) in patients with left ventricular (LV) impairment. We performed a systematic analysis to assess the therapeutic effects of CRT and CRT-D in patients with LV impairment and heart failure., Methods: The Medline database from 1970 to September 2010 was searched. The major outcome examined was the all-cause death rate., Results: A total of 3404 patients were retrieved from seven studies. Overall, CRT-D reduced all-cause death by 8.42% compared with CRT [odds ratio (OR) 0.52, 95% confidence interval (CI) 0.43-0.81, P=0.001, I(2)=63.9%]. An increased benefit was seen after extended follow-up (after 1 year, OR 0.56, CI 0.41-0.77, P=0.0004, I(2)=64.9%), but not after relatively short follow-up (within 1 year, P=0.11). Results from other endpoints examined, such as death from sudden cardiac death and heart failure, also supported CRT-D treatment., Conclusions: Evidence from current randomised and non-randomised trials demonstrates some superiorities of CRT-D over CRT, such as all-cause death rate after one-year follow-up and cardiac death, in patients with LV impairment. However, these findings must be verified in larger, randomised, prospective trials, including with extended patient follow-up., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Aims: To investigate the effects of testosterone treatment on cytokines, ventricular remodeling in rats with heart failure., Materials and Methods: Sprague-Dawley male rats with heart failure were divided into testosterone (n = 22) and placebo (n = 22) group. Pseudo surgery was performed on a third group of 15 male rats as control., Results: Compared with the placebo group, the testosterone group had a greater LVEF (P <0.05), a higher serum IL-10 level (P <0.05) and a lower serum TNF-alpha level (P<0.05). The expression of TNF-alpha mRNA, MMP-9 mRNA and the myocardial hydroxyproline contents in the testosterone group were also lower than in the placebo group (P<0.05). The mortality rate in the testosterone and placebo group was 31.8% and 68.2%, respectively (P <0.05)., Conclusion: Serum testosterone levels were decreased significantly in male rats with heart failure. Testosterone treatment diminishes the imbalance between interleukin-10 and TNF-alpha, suppresses ventricular remodeling and improves cardiac function.

Cardiovascular disease (CVD) and its complications are a leading cause of death worldwide. Endothelial dysfunction plays a crucial role in the initiation and progression of CVD, serving as a pivotal factor in the pathogenesis of cardiovascular, metabolic, and other related diseases. The regulation of endothelial dysfunction is influenced by various risk factors and intricate signaling pathways, which vary depending on the specific disease context. Despite numerous research efforts aimed at elucidating the mechanisms underlying endothelial dysfunction, the precise molecular pathways involved remain incompletely understood. This review elucidates recent research findings on the pathophysiological mechanisms involved in endothelial dysfunction, including nitric oxide availability, oxidative stress, and inflammation‐mediated pathways. We also discuss the impact of endothelial dysfunction on various pathological conditions, including atherosclerosis, heart failure, diabetes, hypertension, chronic kidney disease, and neurodegenerative diseases. Furthermore, we summarize the traditional and novel potential biomarkers of endothelial dysfunction as well as pharmacological and nonpharmacological therapeutic strategies for endothelial protection and treatment for CVD and related complications. Consequently, this review is to improve understanding of emerging biomarkers and therapeutic approaches aimed at reducing the risk of developing CVD and associated complications, as well as mitigating endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Dysregulation of the ubiquitin proteasome system components ubiquitin ligases and proteasome plays an important role in the pathogenesis of cardiac hypertrophy. However, little is known about the role of another ubiquitin proteasome system component, the deubiquitinating enzymes, in cardiac hypertrophy. Here, we revealed a crucial role of ubiquitin specific protease 4 (USP4), a deubiquitinating enzyme prominently expressed in the heart, in attenuating pathological cardiac hypertrophy and dysfunction. USP4 levels were consistently decreased in human failing hearts and in murine hypertrophied hearts. Adenovirus-mediated gain- and loss-of-function approaches indicated that deficiency of endogenous USP4 promoted myocyte hypertrophy induced by angiotensin II in vitro, whereas restoration of USP4 significantly attenuated the prohypertrophic effect of angiotensin II. To corroborate the role of USP4 in vivo, we generated USP4 global knockout mice and mice with cardiac-specific overexpression of USP4. Consistent with the in vitro study, USP4 depletion exacerbated the hypertrophic phenotype and cardiac dysfunction in mice subjected to pressure overload, whereas USP4 transgenic mice presented ameliorated pathological cardiac hypertrophy compared with their control littermates. Molecular analysis revealed that USP4 deficiency augmented the activation of the transforming growth factor β-activated kinase 1 (TAK1)-(JNK1/2)/P38 signaling in response to hypertrophic stress, and blockage of TAK1 activation abolished the pathological effects of USP4 deficiency in vivo. These findings provide the first evidence for the involvement of USP4 in cardiac hypertrophy, and shed light on the therapeutic potential of targeting USP4 in the treatment of cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Objectives: We proposed that the severity of ST-segment elevation myocardial infarction (STEMI) could be classified based on pathophysiological changes. Methods: First-STEMI patients were classified within hospitalization. Grade 0: no detectable myocardial necrosis; Grade 1: myocardial necrosis without functional and morphological abnormalities; Grade 2: myocardial necrosis with reduced LVEF; Grade 3: reduced LVEF on the basis of cardiac remodeling; Grade 4: mitral regurgitation additional to the Grade-3 criteria. Results: Of 180 patients, 1.7, 43.9, 26.1, 23.9 and 4.4% patients were classified as Grade 0 to 4, respectively. The classification is an independent predicator of 90-day MACEs (any death, resuscitated cardiac arrest, acute heart failure and stroke): the rate was 0, 5.1, 8.5, 48.8 and 75% from Grade 0 to 4 (p<0.001), respectively. The Grade-2 patients were more likely to have recovered left ventricular ejection fraction than the Grade-3/4 patients did after 90 days (48.9% vs. 19.1%, p<0.001). Avoiding complicated quantification, the classification served as a good reflection of infarction size as measured by cardiac magnetic resonance imaging (0±0, 15.68±8.48, 23.68±9.32, 36.12±11.35 and 40.66±14.33% of the left ventricular mass by Grade 0 to 4, P<0.001), and with a comparable prognostic value (AUC 0.819 vs. 0.813 for infarction size, p = 0.876 by C-statistics) for MACEs. Conclusions: The new classification represents an easy and objective method to scale the cardiac detriments for STEMI patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The early- to mid-term impact of bone-marrow-derived stem cells (BMC) on diastolic function and exercise capacity after acute myocardial infarction (AMI) remains controversial. We performed a systematic analysis to assess whether BMC transfer is related to an early improvement in diastolic function and exercise capacity after AMI. Methods: Randomized controlled trials (RCTs) of BMC therapy after AMI were extracted from MEDLINE, EMBASE and CENTRAL and analyzed for a change in tissue Doppler annular early (Ea) and late diastolic (Aa) velocities, mitral inflow E velocity to tissue Doppler Ea (E/Ea) ratio, exercise time and exercise capacity. Results: A total of 365 patients were included from 6 trials. A greater improvement was observed in the E/Ea ratio after 1year in the BMC group compared to the control group. Additionally, the BMC-treated patients had a larger improvement in exercise time, ventilation/CO2 production (VE/VCO2 slope) and respiratory exchange ratio (RER) after 1year. Conclusion: The results indicate that intracoronary BMC treatment in AMI patients leads to a mid-term improvement in diastolic function and exercise capacity. [Copyright &y& Elsevier]

Pathological cardiac hypertrophy induced by activation of the renin–angiotensin–aldosterone system (RAAS) is one of the leading causes of heart failure. However, in current clinical practice, the strategy for targeting the RAAS is not sufficient to reverse hypertrophy. Here, we investigated the effect of prostaglandin E1 (PGE1) on angiotensin II (AngII)-induced cardiac hypertrophy and potential molecular mechanisms underlying the effect. Adult male C57 mice were continuously infused with AngII or saline and treated daily with PGE1 or vehicle for two weeks. Neonatal rat cardiomyocytes were cultured to detect AngII-induced hypertrophic responses. We found that PGE1 ameliorated AngII-induced cardiac hypertrophy both in vivo and in vitro. The RNA sequencing (RNA-seq) and expression pattern analysis results suggest that Netrin-1 (Ntn1) is the specific target gene of PGE1. The protective effect of PGE1 was eliminated after knockdown of Ntn1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the PGE1-mediated signaling pathway changes are associated with the mitogen-activated protein kinase (MAPK) pathway. PGE1 suppressed AngII-induced activation of the MAPK signaling pathway, and such an effect was attenuated by Ntn1 knockdown. Blockade of MAPK signaling rescued the phenotype of cardiomyocytes caused by Ntn1 knockdown, indicating that MAPK signaling may act as the downstream effector of Ntn1. Furthermore, inhibition of the E-prostanoid (EP) 3 receptor, as opposed to the EP1, EP2, or EP4 receptor, in cardiomyocytes reversed the effect of PGE1, and activation of EP3 by sulprostone, a specific agonist, mimicked the effect of PGE1. In conclusion, PGE1 ameliorates AngII-induced cardiac hypertrophy through activation of the EP3 receptor and upregulation of Ntn1, which inhibits the downstream MAPK signaling pathway. Thus, targeting EP3, as well as the Ntn1–MAPK axis, may represent a novel approach for treating pathological cardiac hypertrophy. [Display omitted] • PGE1 treatment attenuates AngII-induced cardiac hypertrophy without altering blood pressure. • PGE1 mainly targets cardiomyocytes but not cardiac fibroblasts or CMECs. • The activation of EP3 receptor by PGE1 leads to up-regulation of Ntn1, which inhibits the MAPK signaling pathway. • PGE1-EP3 as well as targeting the Ntn1–MAPK axis may represent a novel treatment for pathological cardiac hypertrophy. [ABSTRACT FROM AUTHOR]