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Background: During pregnancy, significant cardiovascular changes occur to accommodate fetal growth, and catestatin may play a role in these changes. Evidence suggests that catestatin, a pleiotropic sympathoinhibitory peptide, is involved in multiple cardiovascular pathologies, including hypertensive disorders. The objective of this study was to compare serum catestatin levels between first-trimester pregnant women and non-pregnant women, aiming to investigate catestatin's role in blood pressure regulation during early pregnancy. Methods: This cross-sectional study included 72 first-trimester pregnant women and 57 age-matched non-pregnant controls, all without known cardiovascular or metabolic disorders. Results: Serum catestatin concentrations were significantly higher in pregnant women compared to controls (12.4 (9.9–21.2) ng/mL vs. 7.1 (4.5–10.9) ng/mL, p < 0.001). However, there was no significant difference in serum catestatin levels between those with a normal and abnormal uterine artery pulsatility index (17.8 (8.3-22.3) ng/mL vs. 12.5 (9.9–22.4) ng/mL, p = 0.962). Similarly, catestatin concentrations did not significantly differ between primiparous and multiparous women (14.0 (11.5–22.4) ng/mL vs. 10.7 (8.8–19.0) ng/mL). A positive correlation was observed between systolic blood pressure and serum catestatin levels in the control group (r = 0.335, p = 0.011) but not in pregnant women. Conclusions: Research on catestatin in pregnancy is still in its early stages, necessitating further studies to fully elucidate its roles and potential therapeutic applications. [ABSTRACT FROM AUTHOR]

The aim is to assess the levels of circulating catestatin and to establish relationships with various clinical variants of coronary heart disease (CHD) in patients with chronic heart failure (CHF) and concomitant type 2 diabetes mellitus (T2DM) and obesity. Materials and methods. 154 patients were examined, divided into 4 groups according to the presence of metabolic disorders. Group 1 included patients with CHF with CHD and T2DM and obesity (n = 42). The second group consisted of patients with CHF on the background of CHD with T2DM (n = 46), the third group – with accompanying obesity (n = 36), the fourth group was formed from patients who had signs of heart failure of ischemic origin without metabolic disorders (n = 30). The control group consisted of 30 almost healthy persons of comparable age and sex. In addition, patients were divided into subgroups depending on the clinical form of CHD: stable angina, post-infarction cardiosclerosis (PICS) and diffuse cardiosclerosis. Results. Comparing the levels of circulating catestatin in groups 1, 2, 3 and 4, significantly lower levels of catestatin were found in patients with stable angina, compared to patients with diffuse cardiosclerosis by 73.25 %, 66.56 %, 69.86 % and 58.22 %, respectively (р ˂ 0.05). Comparison of catestatin levels revealed a decrease in catestatin levels in patients with stable angina compared to patients with PICS by 64.33 %, 63.70 %, 69.25 %, and 52.02 % in groups 1, 2, 3, and 4, respectively (р ˂ 0.05). Comparison of subgroups of diffuse cardiosclerosis and PICS did not reveal significant changes (р ˃ 0.05) in any group of patients. The indicators of catestatin in the control group had significant differences in the form of an increase in the concentration of the peptide, compared to patients with stable angina pectoris, PICS and diffuse cardiosclerosis in all studied groups (р ˂ 0.05). Evaluation of relationships between serum catestatin levels and clinical variants of coronary heart disease demonstrated a stable inverse relationship between catestatin and stable angina pectoris (r = -0.67, p ˂ 0.05) and PICS (r = -0.42, p ˂ 0.05), and with regard to metabolic diseases, a medium-strength inverse relationship with type 2 diabetes was also established (r = -0.54, p ˂ 0.05). Conclusions. The concentration of catestatin in blood serum had the lowest values in the group of patients with chronic heart failure of ischemic origin with concomitant diabetes mellitus type 2 and obesity, compared to the isolated course of chronic heart failure (p ˂ 0.05), which confirms the anti-inflammatory effects of catestatin and its connection with the insulin resistance progression. Among the clinical variants of coronary heart disease, the lowest levels of catestatin were demonstrated by patients with stable angina pectoris and post-infarction cardiosclerosis (r = -0.67 and r = -0.42, p ˂ 0.05, respectively), which indicates the association of this biomarker with various clinical variants of coronary heart disease.

The rapid increase in drug-resistant and multidrug-resistant infections poses a serious challenge to antimicrobial therapies, and has created a global health crisis. Since antimicrobial peptides (AMPs) have escaped bacterial resistance throughout evolution, AMPs are a category of potential alternatives for antibiotic-resistant "superbugs". The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372; bCgA344-364) was initially identified in 1997 as an acute nicotinic-cholinergic antagonist. Subsequently, CST was established as a pleiotropic hormone. In 2005, it was reported that N-terminal 15 amino acids of bovine CST (bCST1-15 aka cateslytin) exert antibacterial, antifungal, and antiyeast effects without showing any hemolytic effects. In 2017, D-bCST1-15 (where L-amino acids were changed to D-amino acids) was shown to exert very effective antimicrobial effects against various bacterial strains. Beyond antimicrobial effects, D-bCST1-15 potentiated (additive/synergistic) antibacterial effects of cefotaxime, amoxicillin, and methicillin. Furthermore, D-bCST1-15 neither triggered bacterial resistance nor elicited cytokine release. The present review will highlight the antimicrobial effects of CST, bCST1-15 (aka cateslytin), D-bCST1-15, and human variants of CST (Gly364Ser-CST and Pro370Leu-CST); evolutionary conservation of CST in mammals; and their potential as a therapy for antibiotic-resistant "superbugs".

Background Cardiovascular disease remains one of the leading causes of death globally. Myocardial ischemia and infarction, in particular, frequently cause disturbances in cardiac electrical activity that can trigger ventricular arrhythmias. We aimed to investigate whether catestatin, an endogenous catecholamine‐inhibiting peptide, ameliorates myocardial ischemia‐induced ventricular arrhythmias in rats and the underlying ionic mechanisms. Methods and Results Adult male Sprague‐Dawley rats were randomly divided into control and catestatin groups. Ventricular arrhythmias were induced by ligation of the left anterior descending coronary artery and electrical stimulation. Action potential, transient outward potassium current, delayed rectifier potassium current, inward rectifying potassium current, and L‐type calcium current (ICa‐L) of rat ventricular myocytes were recorded using a patch‐clamp technique. Catestatin notably reduced ventricular arrhythmia caused by myocardial ischemia/reperfusion and electrical stimulation of rats. In ventricular myocytes, catestatin markedly shortened the action potential duration of ventricular myocytes, which was counteracted by potassium channel antagonists TEACl and 4‐AP, and ICa‐L current channel agonist Bay K8644. In addition, catestatin significantly increased transient outward potassium current, delayed rectifier potassium current, and inward rectifying potassium current density in a concentration‐dependent manner. Catestatin accelerated the activation and decelerated the inactivation of the transient outward potassium current channel. Furthermore, catestatin decreased ICa‐L current density in a concentration‐dependent manner. Catestatin also accelerated the inactivation of the ICa‐L channel and slowed down the recovery of ICa‐L from inactivation. Conclusions Catestatin enhances the activity of transient outward potassium current, delayed rectifier potassium current, and inward rectifying potassium current, while suppressing the ICa‐L in ventricular myocytes, leading to shortened action potential duration and ultimately reducing the ventricular arrhythmia in rats.

Background: During pregnancy, significant cardiovascular changes occur to accommodate fetal growth, and catestatin may play a role in these changes. Evidence suggests that catestatin, a pleiotropic sympathoinhibitory peptide, is involved in multiple cardiovascular pathologies, including hypertensive disorders. The objective of this study was to compare serum catestatin levels between first-trimester pregnant women and non-pregnant women, aiming to investigate catestatin’s role in blood pressure regulation during early pregnancy. Methods: This cross-sectional study included 72 first-trimester pregnant women and 57 age-matched non-pregnant controls, all without known cardiovascular or metabolic disorders. Results: Serum catestatin concentrations were significantly higher in pregnant women compared to controls (12.4 (9.9–21.2) ng/mL vs. 7.1 (4.5–10.9) ng/mL, p < 0.001). However, there was no significant difference in serum catestatin levels between those with a normal and abnormal uterine artery pulsatility index (17.8 (8.3-22.3) ng/mL vs. 12.5 (9.9–22.4) ng/mL, p = 0.962). Similarly, catestatin concentrations did not significantly differ between primiparous and multiparous women (14.0 (11.5–22.4) ng/mL vs. 10.7 (8.8–19.0) ng/mL). A positive correlation was observed between systolic blood pressure and serum catestatin levels in the control group (r = 0.335, p = 0.011) but not in pregnant women. Conclusions: Research on catestatin in pregnancy is still in its early stages, necessitating further studies to fully elucidate its roles and potential therapeutic applications.

Preeclampsia (PE) is a unique pregnancy disorder affecting women across the world. It is characterized by the new onset of hypertension with coexisting end-organ damage. Although the disease has been known for centuries, its exact pathophysiology and, most importantly, its prevention remain elusive. The basis of its associated molecular changes has been attributed to the placenta and the hormones regulating its function. One such hormone is chromogranin A (CgA). In the placenta, CgA is cleaved to form a variety of biologically active peptides, including catestatin (CST), known inter alia for its vasodilatory effects. Recent studies indicate that the CST protein level is diminished both in patients with hypertension and those with PE. Therefore, the aim of the present paper is to review the most recent and most relevant in vitro, in vivo, and clinical studies to provide an overview of the proposed impact of CST on the molecular processes of PE and to consider the possibilities for future experiments in this area. [ABSTRACT FROM AUTHOR]

Catestatin (CST) is a pleiotropic peptide with cardioprotective and metabolic effects. CST is involved in the pathogenesis of both arterial hypertension (AH) and type 2 diabetes mellitus (T2DM), which are the risk factors of cardiovascular diseases. In this study, we aimed to investigate the plasma CST levels in hypertensive patients, especially with T2DM, as well as compare those with healthy volunteers, and explore the relationship between CST levels and clinical, anthropometric and laboratory parameters. 106 Hypertensive patients, 55 of which had comorbidity T2DM, and 30 healthy volunteers were enrolled in the study. All subjects underwent clinical examination, including vital signs and anthropometric data assessment, medical history interview, and blood sample collection. Plasma CST levels were measured by an enzyme-linked immunosorbent assay (ELISA), using a commercial diagnostic kit. The plasma CST levels were significantly lower in hypertensive patients (N = 106) compared with healthy subjects (N = 30) (5.02 ± 1.09 vs. 6.64 ± 0.72; p < 0.001). Furthermore, hypertensive patients with T2DM (N = 55) have significantly reduced CST levels in comparison with those without T2DM (N = 51) (4.47 ± 1.16 vs. 5.61 ± 0.61; p < 0.001). CST significantly correlated with anthropometric characteristics, in particular, weight (r = − 0.344; p < 0.001), BMI (r = − 0.42; p < 0.001), neck (r = − 0.358; p < 0.001), waist (r = − 0.487; p < 0.001), hip (r = − 0.312; p < 0.001), wrist circumferences (r = − 0.264; p = 0.002), and waist-to-hip ratio (r = − 0.395; p < 0.001). Due to its antihypertensive effect, CST has significant associations with systolic BP (r = − 0.475; p < 0.001) and duration of AH (r = − 0.26; p = 0.007). CST also has an inverse relationship with insulin (r = − 0.382; p < 0.001), glucose (r = − 0.45; p < 0.001), index HOMA-IR (r = − 0.481; p < 0.001) and HbA1c (r = − 0.525; p < 0.001), that indicate its involvement in T2DM development. Besides, CST has significant correlations with uric acid levels (r = − 0.412; p < 0.001) as well as lipid parameters, especially HDL-C (r = 0.480; p < 0.001), VLDL-C (r = − 0.238; p = 0.005), TG (r = − 0.4; p < 0.001), non-HDL-C/HDL-C (r = − 0.499; p < 0.001). Multiple linear regression analysis indicated BMI (β = − 0.22; p = 0.007), AH duration (β = − 0.25; p = 0.008), HbA1c (β = − 0.43; p = 0.019) and HDL-C levels (β = 0.27; p = 0.001) as independent predictors of CST levels. The hypertensive patients have significantly decreased CST levels that are even more reduced in the presence of comorbid T2DM. The established correlations with anthropometric and laboratory parameters indicate not only antihypertensive but also metabolic effects of CST. Our results suggest the probable role of CST in the pathophysiology of cardiometabolic diseases and the development of cardiovascular complications. [ABSTRACT FROM AUTHOR]

Catestatin (CST) is a bioactive cleavage product of the neuroendocrine prohormone chromogranin A (CgA). Recent findings show that CST can exert anti-inflammatory and antiadrenergic effects by suppressing the inflammatory actions of mammalian macrophages. However, recent findings also suggest that macrophages themselves are major CST producers. Here, we hypothesize that macrophages produce CST in an inflammation-dependent manner and thereby might self-regulate inflammation in an autocrine fashion. CST is associated with pathological conditions hallmarked by chronic inflammation, including autoimmune, cardiovascular, and metabolic disorders. Since intraperitoneal injection of CST in mouse models of diabetes and inflammatory bowel disease has been reported to be beneficial for mitigating disease, we posit that CST should be further investigated as a candidate target for treating certain inflammatory diseases.

AimsAging is associated with the development of insulin resistance and hypertension which may stem from inflammation induced by accumulation of toxic bacterial DNA crossing the gut barrier. The aim of this study was to identify factors counter-regulating these processes. Taking advantage of the Chromogranin A (CgA) knockout (CgA-KO) mouse as a model for healthy aging, we have identified Vsig4 (V-set and immunoglobulin domain containing 4) as the critical checkpoint gene in offsetting age-associated hypertension and diabetes.Methods and resultsThe CgA-KO mice display two opposite aging phenotypes: hypertension but heightened insulin sensitivity at young age, whereas the blood pressure normalizes at older age and insulin sensitivity further improves. In comparison, aging WT mice gradually lost glucose tolerance and insulin sensitivity and developed hypertension. The gut barrier, compromised in aging WT mice, was preserved in CgA KO mice leading to major 35-fold protection against bacterial DNA-induced inflammation. Similarly, RNA sequencing showed increased expression of the Vsig4 gene (which removes bacterial DNA) in the liver of 2-yr-old CgA-KO mice, which may account for the very low accumulation of microbial DNA in the heart. The reversal of hypertension in aging CgA-KO mice likely stems from (i) low accumulation of microbial DNA, (ii) decreased spillover of norepinephrine in the heart and kidneys, and (iii) reduced inflammation.ConclusionWe conclude that healthy aging relies on protection from bacterial DNA and the consequent low inflammation afforded by CgA-KO. Vsig4 also plays a crucial role in "healthy aging" by counteracting age-associated insulin resistance and hypertension.

The objective: to investigate the impact of hypertensive disease (HD) and concomitant type 2 diabetes mellitus (T2DM) on the quality of life (QOL) of patients using the SF-36 questionnaire and to evaluate the peculiarities of the QOL parameters depending on plasma relaxin-2 (RLN-2) and catestatin (CTS) levels. Materials and methods. The study was conducted in accordance with the principles of the Declaration of Helsinki. 136 patients took part in the study: 106 patients with HD and 30 healthy volunteers. The patients with HD were divided into two groups. The first group included 55 patients with HD and T2DM, the second group - 51 persons with HD without T2DM. Each study participant underwent a comprehensive clinical, laboratory and instrumental examinations. All participants filled out quality of life SF-36 questionnaire and the questionary of HD patient. Concentrations of CTS and RLN-2 in blood plasma were determined by enzyme immunoassay method (E4996Hu, BT Lab, Shanghai, China and E-EL-H1582, Elabscience, USA, respectively). All patients filled the home blood pressure monitoring diaries for 31 days. Statistical data analysis was performed using the SPSS 25.0 statistical program. Results. The patients with HD had lower parameters of physical and mental components of health compared to healthy volunteers (p<0.005). It was found that the presence of concomitant T2DM leads to even a greater decrease in quality of life indicators than in patients with HD without carbohydrate metabolism disorders (p<0.05). In patients with RLN-2 levels ≥4.69 pg/ml the lower parameters of the physical component of health (p<0.05) and social functioning (p=0.012) were determined. Lower CTS scores are associated with lower QOL scores (p≤0.005). Significant negative correlations were found between average SBP (aSBP) and indicators of physical and mental components of health (p<0.001), while mean DBP had correlations only with general health and total physical component of health (p<0.05). Conclusions. HD leads to a decreased QOL of patients, which is confirmed by lower scores of the SF-36 questionnaire and established negative correlations between aSBP and QOL parameters. The presence of concomitant T2DM is associated with even a greater decline in physical and mental health components. [ABSTRACT FROM AUTHOR]

AimA "leaky" gut barrier has been implicated in the initiation and progression of a multitude of diseases, for example, inflammatory bowel disease (IBD), irritable bowel syndrome and celiac disease. Here we show how pro-hormone Chromogranin A (CgA), produced by the enteroendocrine cells, and Catestatin (CST: hCgA352-372 ), the most abundant CgA-derived proteolytic peptide, affect the gut barrier.MethodsColon tissues from region-specific CST-knockout (CST-KO) mice, CgA-knockout (CgA-KO) and WT mice were analysed by immunohistochemistry, western blot, ultrastructural and flowcytometry studies. FITC-dextran assays were used to measure intestinal barrier function. Mice were supplemented with CST or CgA fragment pancreastatin (PST: CgA250-301 ). The microbial composition of cecum was determined. CgA and CST levels were measured in blood of IBD patients.ResultsPlasma levels of CST were elevated in IBD patients. CST-KO mice displayed (a) elongated tight, adherens junctions and desmosomes similar to IBD patients, (b) elevated expression of Claudin 2, and (c) gut inflammation. Plasma FITC-dextran measurements showed increased intestinal paracellular permeability in the CST-KO mice. This correlated with a higher ratio of Firmicutes to Bacteroidetes, a dysbiotic pattern commonly encountered in various diseases. Supplementation of CST-KO mice with recombinant CST restored paracellular permeability and reversed inflammation, whereas CgA-KO mice supplementation with CST and/or PST in CgA-KO mice showed that intestinal paracellular permeability is regulated by the antagonistic roles of these two peptides: CST reduces and PST increases permeability.ConclusionThe pro-hormone CgA regulates the intestinal paracellular permeability. CST is both necessary and sufficient to reduce permeability and primarily acts by antagonizing PST.

Background. Hypertension is the major pandemic in human history, which determines the structure of cardiovascular morbidity and mortality. There is an obvious relationship between hypertension and various diseases that largely determine its development and increase the risk of cardiovascular complications. Neuropeptides appear to have a major impact on the progression of these complications. Catestatin (CST) is one of them, which deserves special scientific and practical concern, as it has a wide range of biological effects in the body. The aim of the study: to determine the place of CST in the early diagnosis of cardiovascular and metabolic complications in patients with comorbid hypertension among the Ukrainian population. Materials and methods. One hundred and eleven patients with hypertension, type 2 diabetes mellitus, obesity (men/women — 50/61) and 20 controls were examined. All patients with hypertension, type 2 diabetes mellitus, and obesity were aged 54.37 ± 1.18 years. Following a thorough examination and supervision, they were divi­ded into 2 groups depending on the median CST level of 2.45 ng/ml. The first group included 55 (49.5 %) patients who had a CST level below 2.45 ng/ml, the second one consisted of 56 patients (50.5 %) who had a CST level above 2.45 ng/ml. In all patients, we measured body weight, height, calculated body mass index, evaluated glycated hemoglobin levels, lipid metabolism (serum concentrations of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein cholesterol); systolic and diastolic blood pressure. The content of CST, cardiotrophin 1, leptin, cystatin C, neutrophil gelatinase-associated lipocalin, N-terminal prohormone of brain natriuretic peptide, 25(OH)D, β2-microglobulin, and insulin levels in the blood serum were determined by enzyme-linked immunosorbent assay. Results. A reliable difference between the groups was found by β2-microglobulin (p = 0.008). Univariate and multivariate linear regression analysis revealed a negative correlation between CST and cardiotrophin 1, N-terminal prohormone of brain natriuretic peptide, neutrophil gelatinase-associated lipocalin, and 25(OH)D. A positive correlation was found between CST and the level of glycated hemoglobin, body mass index, and triglycerides. A statistically significant correlation was found between CST and creatinine (R = –0.21, p = 0.029), high-density lipoprotein cholesterol (R = 0.207, p = 0.029), and β2-microglobulin (R = 0.279, p = 0.0029) in the patients with hypertension. Conclusions. It has been proven that a decrease in serum catestatin concentration can be a risk factor for the development of more severe comorbidities in patients with hypertension. The detected relationships of catestatin with creatinine, urea, and β2-microglobulin suggest that CST is a predictor of chronic kidney disease in patients with comorbidities. The revealed correlation of CST with high-density lipoprotein, obesity, and body mass index suggests its importance in the prevention of atherosclerotic and metabolic complications in patients with hypertension, type 2 diabetes mellitus, and obesity.

Aim. In patients with non-obstructive coronary artery disease (CAD), to evaluate the pathophysiological significance and diagnostic effectiveness of catestatin in detecting heart failure with preserved ejection fraction (HFpEF), as well as to assess the relationship of the levels of this biomarker with heart rate variability (HRV) parameters and the severity of diastolic dysfunction.Material and methods. The study included 83 patients (44 men, mean age, 62,0 [57,0; 68,5] years) with non-obstructive CAD and preserved left ventricular (LV) ejection fraction of 63 [60; 64]%). Echocardiography was performed according to a standard protocol. HRV was assessed using 24-hour electrocardiographic monitoring. Serum biomarker levels were determined using enzyme-linked immunosorbent assay.Results. Patients were divided into groups depending on HFpEF presence: group 1 (n=63) included patients with newly diagnosed HFpEF, and group 2 included patients without heart failure (n=20). Serum catestatin concentrations were 43,1% lower (p

Background: Catestatin has been identified as an important factor in blood pressure control in non-pregnant adults. A possible impact on the development of hypertensive disorders of pregnancy has been indicated. Data on catestatin levels in pregnancy are scarce. The aim of this study was to investigate a potential association of maternal serum catestatin levels to the pathogenesis of preeclampsia. Methods: We evaluated serum catestatin levels of 50 preeclamptic singleton pregnancies and 50 healthy gestational-age-matched pregnancies included in the obstetric biobank registry of the Medical University of Vienna. Receiver operating characteristic curves and logistic regression models were performed to investigate an association between catestatin levels and development of preeclampsia. Results: Catestatin levels were significantly decreased in women with preeclampsia compared to healthy controls (median CST: 3.03 ng/mL, IQR [1.24–7.21 ng/mL] vs. 4.82 ng/mL, IQR [1.82–10.02 ng/mL]; p = 0.010), indicating an association between decreased catestatin values and the development of preeclampsia. There was no significant difference in catestatin values between early-onset preeclampsia and late-onset preeclampsia. Modelling the occurrence of preeclampsia via logistic regression was improved when adding catestatin as a predictive factor. Conclusions: Decreased serum catestatin levels are associated with the presence of preeclampsia. Further investigations into the diagnostic value and possible therapeutic role of catestatin in preeclampsia are warranted. [ABSTRACT FROM AUTHOR]

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The epidemic of heart failure (HF) is one of the problems that the global health system has been facing for decades. HF is a multicomponent clinical syndrome caused by dysfunction of the heart and its pathological remodeling. In addition to the well-known natriuretic peptides, a number of cardiovascular biological markers have now been identified that provide clinicians with additional opportunities in diagnosing, classifying, predicting, and monitoring the effectiveness of treating patients with HF. From the position of establishing the sympathetic load in patients with HF, it seems very promising to assess the concentrations of catestatin. The presented data of our literature review suggest that catestatin is probably a reliable biological marker of the activity of the sympathetic division of the autonomic nervous system, and its elevated concentrations in patients with HF reflect the severity of the pathological process. However, despite the reliable results of studies, the clinical significance of assessing the values of this marker both separately and in the framework of a multimarker model requires further study in larger prospective clinical studies.

Catestatin (CST) is a metabolite of chromogranin A, a soluble protein in catecholamine storage vesicles acting as a feedback inhibitor of catecholamine secretion. This study aims to investigate the correlation of catestatin with dipper and non-dipper status in hypertensive patients. Hypertensive (n=355) and healthy subjects (n=129) were randomly selected at an outpatient clinic. Blood pressure and heart rate were measured according to relevant guidelines. Plasma catestatin level, plasma glucose, lipid levels were measured. An ambulatory blood pressure monitor was performed to determine the dipping patterns in hypertensive subjects. Univariate and multivariate analyses were conducted to assess factors affecting catestatin levels. Left ventricular mass was higher among hypertensives compared with healthy controls (178±47 g versus 213±52 g in healthy controls and hypertensives, p [Med-Science 2022; 11(4.000): 1402-8]

Background: Catestatin (Cts) is a peptide derived from proteolytic cleavage of chromogranin A, which exhibits cardioprotective and anti-inflammatory properties. Cts has been proposed as a potential biomarker for cardiovascular (CV) disease. Objectives: examining Cts in patients with incidentally discovered adrenocortical adenomas (AI), and its associations with CV risk factors and blood pressure (BP). Materials and methods: In this cross-sectional study, 64 AI patients without overt CV disease other than primary hypertension were recruited along with 24 age-, sex-, and body-mass-index (BMI)-matched controls with normal adrenal morphology. Laboratory, 24-h ambulatory BP monitoring, echocardiography, and common carotid artery sonography examinations were performed. Results: Unadjusted Cts was higher in AI patients (median 6.5, interquartile range: 4.9-37 ng/ml) versus controls (4.5 (3.5 - 28)), p=0.048, however, the difference was insignificant after adjusting for confounding variables. Cts was lower in subjects with metabolic syndrome than in those without it (5.2 (3.9-6.9) vs. 25.7 (5.8-115) ng/ml, p<0.01), and in men compared to women (4.9 (4-7.4) ng/ml vs. 7 (4.8-100), p=0.015). AI patients in the lower half of Cts levels compared to those in the upper had a higher prevalence of hypertension (OR 0.15, 95% CI: 0.041-0.5, p<0.001) and metabolic syndrome (OR 0.15, 95% CI 0.041-0.5, p<0.001). In AI patients Cts correlated positively with high-density lipoprotein cholesterol (Spearman's r=0.31), negatively with BMI (r=-0.31), and 10-year atherosclerotic CV disease risk (r=-0.42). Conclusions: Our data indicate associations between CV risk factors and Cts. More clinical research is needed to apply serum Cts as a biomarker. [ABSTRACT FROM AUTHOR]

The primary objective of the study was to evaluate the prognostic value of measuring plasma catestatin (CST) concentration in patients with heart failure with reduced ejection fraction (HFrEF) as a predictor of unplanned hospitalization and all-cause death independently and as a composite endpoint at 2-year follow-up. The study group includes 122 hospitalized Caucasian patients in NYHA classes II to IV. Patients who died during the 24-month follow-up period (n = 44; 36%) were significantly older on the day of enrollment, were more likely to be in a higher NYHA class, had lower TAPSE, hemoglobin concentration, hematocrit, and platelet count, higher concentrations of CST, NT-proBNP, troponin T, creatinine, and glucose, and higher red cell distribution width value and leukocyte and neutrocyte count than patients who survived the follow-up period. Plasma catestatin concentration increased with NYHA class (R = 0.58; p <0.001) and correlated significantly with blood NT-proBNP concentration (R = 0.44; p <0.001). We showed that higher plasma catestatin concentration increased the risk of all-cause death by more than five times. Plasma CST concentration is a valuable prognostic parameter in predicting death from all causes and unplanned hospitalization in patients with HFrEF. [ABSTRACT FROM AUTHOR]

Background. Hypertension is the major pandemic in human history, which determines the structure of cardiovascular morbidity and mortality. There is an obvious relationship between hypertension and various diseases that largely determine its development and increase the risk of cardiovascular complications. Neuropeptides appear to have a major impact on the progression of these complications. Catestatin (CST) is one of them, which deserves special scientific and practical concern, as it has a wide range of biological effects in the body. The aim of the study: to determine the place of CST in the early diagnosis of cardiovascular and metabolic complications in patients with comorbid hypertension among the Ukrainian population. Materials and methods. One hundred and eleven patients with hypertension, type 2 diabetes mellitus, obesity (men/women - 50/61) and 20 controls were examined. All patients with hypertension, type 2 diabetes mellitus, and obesity were aged 54.37 ± 1.18 years. Following a thorough examination and supervision, they were divided into 2 groups depending on the median CST level of 2.45 ng/ml. The first group included 55 (49.5 %) patients who had a CST level below 2.45 ng/ml, the second one consisted of 56 patients (50.5 %) who had a CST level above 2.45 ng/ml. In all patients, we measured body weight, height, calculated body mass index, evaluated glycated hemoglobin levels, lipid metabolism (serum concentrations of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, and very low-density lipoprotein cholesterol); systolic and diastolic blood pressure. The content of CST, cardiotrophin 1, leptin, cystatin C, neutrophil gelatinase-associated lipocalin, N-terminal prohormone of brain natriuretic peptide, 25(OH)D, β2-microglobulin, and insulin levels in the blood serum were determined by enzyme-linked immunosorbent assay. Results. A reliable difference between the groups was found by β2-microglobulin (p = 0.008). Univariate and multivariate linear regression analysis revealed a negative correlation between CST and cardiotrophin 1, N-terminal prohormone of brain natriuretic peptide, neutrophil gelatinase-associated lipocalin, and 25(OH)D. A positive correlation was found between CST and the level of glycated hemoglobin, body mass index, and triglycerides. A statistically significant correlation was found between CST and creatinine (R = -0.21, p = 0.029), high-density lipoprotein cholesterol (R = 0.207, p = 0.029), and β2-microglobulin (R = 0.279, p = 0.0029) in the patients with hypertension. Conclusions. It has been proven that a decrease in serum catestatin concentration can be a risk factor for the development of more severe comorbidities in patients with hypertension. The detected relationships of catestatin with creatinine, urea, and β2-microglobulin suggest that CST is a predictor of chronic kidney disease in patients with comorbidities. The revealed correlation of CST with high-density lipoprotein, obesity, and body mass index suggests its importance in the prevention of atherosclerotic and metabolic complications in patients with hypertension, type 2 diabetes mellitus, and obesity. [ABSTRACT FROM AUTHOR]

Chromogranin A (ChgA) is an acidic pro-protein found in neuroendocrine organs, pheochromocytoma chromaffin granules, and tumor cells. Proteolytic processing of ChgA gives rise to an array of biologically active peptides such as pancreastatin (PST), vasostatin, WE14, catestatin (CST), and serpinin, which have diverse roles in regulating cardiovascular functions and metabolism, as well as inflammation. Intricate tissue-specific role of ChgA-derived peptide activity in preclinical rodent models of metabolic syndrome reveals complex effects on carbohydrate and lipid metabolism. Indeed, ChgA-derived peptides, PST and CST, play a pivotal role in metabolic syndrome such as obesity, insulin resistance, and diabetes mellitus. Additionally, supplementation of specific peptide in ChgA-KO mice have an opposing effect on physiological functions, such as PST supplementation reduces insulin sensitivity and enhances inflammatory response. In contrast, CST supplementation enhances insulin sensitivity and reduces inflammatory response. In this review, we focus on the tissue-specific role of PST and CST as therapeutic targets in regulating carbohydrate and lipid metabolism, along with the associated risk factors. [ABSTRACT FROM AUTHOR]

BackgroundCatestatin (Cts) is a peptide derived from proteolytic cleavage of chromogranin A, which exhibits cardioprotective and anti-inflammatory properties. Cts has been proposed as a potential biomarker for cardiovascular (CV) disease.Objectivesexamining Cts in patients with incidentally discovered adrenocortical adenomas (AI), and its associations with CV risk factors and blood pressure (BP).Materials and methodsIn this cross-sectional study, 64 AI patients without overt CV disease other than primary hypertension were recruited along with 24 age-, sex-, and body-mass-index (BMI)-matched controls with normal adrenal morphology. Laboratory, 24-h ambulatory BP monitoring, echocardiography, and common carotid artery sonography examinations were performed.ResultsUnadjusted Cts was higher in AI patients (median 6.5, interquartile range: 4.9-37 ng/ml) versus controls (4.5 (3.5 – 28)), p=0.048, however, the difference was insignificant after adjusting for confounding variables. Cts was lower in subjects with metabolic syndrome than in those without it (5.2 (3.9- 6.9) vs. 25.7 (5.8-115) ng/ml, p

Background Catestatin has been reported as a pleiotropic cardioprotective peptide. Heart failure with preserved ejection fraction (HFpEF) was considered a heterogeneous syndrome with a complex cause. We sought to investigate the role of catestatin in HFpEF and diastolic dysfunction. METHODS AND RESULTS Administration of recombinant catestatin (1.5 mg/kg/d) improved diastolic dysfunction and left ventricular chamber stiffness in transverse aortic constriction mice with deoxycorticosterone acetate pellet implantation, as reflected by Doppler tissue imaging and pressure‐volume loop catheter. Less cardiac hypertrophy and myocardial fibrosis was observed, and transcriptomic analysis revealed downregulation of mitochondrial electron transport chain components after catestatin treatment. Catestatin reversed mitochondrial structural and respiratory chain component abnormality, decreased mitochondrial proton leak, and reactive oxygen species generation in myocardium. Excessive oxidative stress induced by Ru360 abolished catestatin treatment effects on HFpEF‐like cardiomyocytes in vitro, indicating the beneficial role of catestatin in HFpEF as a mitochondrial ETC modulator. The serum concentration of catestatin was tested among 81 patients with HFpEF and 76 non–heart failure controls. Compared with control subjects, serum catestatin concentration was higher in patients with HFpEF and positively correlated with E velocity to mitral annular e′ velocity ratio, indicating a feedback compensation role of catestatin in HFpEF. Conclusions Catestatin protects against diastolic dysfunction in HFpEF through attenuating mitochondrial electron transport chain–derived reactive oxygen species generation. Serum catestatin concentration is elevated in patients with HFpEF, probably as a relatively insufficient but self‐compensatory mechanism.

One of the most dangerous complications of pregnancy is preeclampsia (PE), a disease associated with a high risk of maternal and fetal mortality and morbidity. Although its etiology remains unknown, the placenta is believed to be at the center of ongoing changes. One of the hormones produced by the placenta is chromogranin A (CgA). Thus far, its role in pregnancy and pregnancy-related disorders is enigmatic, yet it is known that both CgA and its derived peptide catestatin (CST) are involved in the majority of the processes that are disturbed in PE, such as blood pressure regulation or apoptosis. Therefore, in this study, the influence of the preeclamptic environment on the production of CgA using two cell lines, HTR-8/SVneo and BeWo, was investigated. Furthermore, the capacity of trophoblastic cells to secrete CST to the environment was tested, as well as the correlation between CST and apoptosis. This study provided the first evidence that CgA and CST proteins are produced by trophoblastic cell lines and that the PE environment has an impact on CST protein production. Furthermore, a strong negative correlation between CST protein level and apoptosis induction was found. Hence, both CgA and its derived peptide CST may play roles in the complex process of PE pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Along with decreased sympatho-adrenal flow, catestatin has a number of cardiovascular effects. Reduced plasma catestatin levels could be a sign of a predisposition to develop metabolic and hypertensive diseases. Aim and objectives: To assess the function of catestatin in cardiometabolic risk assessment among diabetic children. Subjects and methods: This case-control study was carried out on 108 children at Pediatrics Department, Zagazig University Hospital. Children were divided into 2 groups: (Group A): Case group 54 children with diabetes, (Group B): Control group 54 apparent healthy children at same sex and age. Every infant was subjected to serum catestatin concentrations measurement using ELISA Kit. Result: Median Catestatin in diabetic group was 8.35 ng/ml (6.16 - 17.41) while that for Control group was 11.19 ng/dl(7.42 -16.56), the difference was statistically significant (p< 0.05). Conclusion: Serum Catestatin was related to diabetes and it cannot be considered as a good biomarker of cardio metabolic risk among diabetic children. Further larger scale studies are needed to confirm our results. [ABSTRACT FROM AUTHOR]

Pregnancy is a state of physiological and hormonal changes. One of the endocrine factors involved in these processes is chromogranin A, an acidic protein produced, among others, by the placenta. Although it has been previously linked to pregnancy, no existing articles have ever managed to clarify the role of this protein regarding this subject. Therefore, the aim of the present study is to gather knowledge of chromogranin A's function with reference to gestation and parturition, clarify elusive information, and, most importantly, to formulate hypotheses for the future studies to verify. [ABSTRACT FROM AUTHOR]

Human chromogranin A (CgA), a 439 residue-long member of the "granin" secretory protein family, is the precursor of several peptides and polypeptides involved in the regulation of the innate immunity, cardiovascular system, metabolism, angiogenesis, tissue repair, and tumor growth. Despite the many biological activities observed in experimental and preclinical models for CgA and its most investigated fragments (vasostatin-I and catestatin), limited information is available on the receptor mechanisms underlying these effects. The interaction of vasostatin-1 with membrane phospholipids and the binding of catestatin to nicotinic and b2-adrenergic receptors have been proposed as important mechanisms for some of their effects on the cardiovascular and sympathoadrenal systems. Recent studies have shown that neuropilin-1 and certain integrins may also work as high-affinity receptors for CgA, vasostatin-1 and other fragments. In this case, we review the results of these studies and discuss the structural requirements for the interactions of CgA-related peptides with neuropilin-1 and integrins, their biological effects, their mechanisms, and the potential exploitation of compounds that target these ligand-receptor systems for cancer diagnosis and therapy. The results obtained so far suggest that integrins (particularly the integrin avb6) and neuropilin-1 are important receptors that mediate relevant pathophysiological functions of CgA and CgA fragments in angiogenesis, wound healing, and tumor growth, and that these interactions may represent important targets for cancer imaging and therapy. [ABSTRACT FROM AUTHOR]

Catestatin (CST) is a metabolite of chromogranin A, a soluble protein in catecholamine storage vesicles acting as a feedback inhibitor of catecholamine secretion. This study aims to investigate the correlation of catestatin with dipper and non-dipper status in hypertensive patients. Hypertensive (n=355) and healthy subjects (n=129) were randomly selected at an outpatient clinic. Blood pressure and heart rate were measured according to relevant guidelines. Plasma catestatin level, plasma glucose, lipid levels were measured. An ambulatory blood pressure monitor was performed to determine the dipping patterns in hypertensive subjects. Univariate and multivariate analyses were conducted to assess factors affecting catestatin levels. Left ventricular mass was higher among hypertensives compared with healthy controls (178±47 g versus 213±52 g in healthy controls and hypertensives, p<0.05), but there was no significant difference between the two hypertensive groups 205±43 g versus 228±77 g in dippers versus non-dippers, p=0.54). Average systolic blood pressure (SBP) and the percentage of systolic blood pressure dipping were statistically significantly negative correlated with CST (r=-0.316, p<0.05 for systolic dipping%, r=-0.283, p<0.05 for ASBP). In multivariate analysis for the prediction of catestatin levels, systolic dipping % and mean SBP were found to be independent predictors of plasma catestatin level. Plasma catestatin levels were lower among hypertensives compared to healthy controls and modest inverse correlations between catestatin and dipping percentage of systolic blood pressure and also between catestatin and average systolic blood pressure were noted. In hypertensive subjects, lower plasma catestatin levels may alert clinicians to the non-dipping status of the blood pressure. [ABSTRACT FROM AUTHOR]

Aims: Aging is associated with the development of insulin resistance and hypertension which may stem from inflammation induced by accumulation of toxic bacterial DNA crossing the gut barrier. The aim of this study was to identify factors counter-regulating these processes. Taking advantage of the Chromogranin A (CgA) knockout (CgA-KO) mouse as a model for healthy aging, we have identified Vsig4 (V-set and immunoglobulin domain containing 4) as the critical checkpoint gene in offsetting age-associated hypertension and diabetes. Methods and Results: The CgA-KO mice display two opposite aging phenotypes: hypertension but heightened insulin sensitivity at young age, whereas the blood pressure normalizes at older age and insulin sensitivity further improves. In comparison, aging WT mice gradually lost glucose tolerance and insulin sensitivity and developed hypertension. The gut barrier, compromised in aging WT mice, was preserved in CgA KO mice leading to major 35-fold protection against bacterial DNA-induced inflammation. Similarly, RNA sequencing showed increased expression of the Vsig4 gene (which removes bacterial DNA) in the liver of 2-yr-old CgA-KO mice, which may account for the very low accumulation of microbial DNA in the heart. The reversal of hypertension in aging CgA-KO mice likely stems from (i) low accumulation of microbial DNA, (ii) decreased spillover of norepinephrine in the heart and kidneys, and (iii) reduced inflammation. Conclusion: We conclude that healthy aging relies on protection from bacterial DNA and the consequent low inflammation afforded by CgA-KO. Vsig4 also plays a crucial role in "healthy aging" by counteracting age-associated insulin resistance and hypertension. [ABSTRACT FROM AUTHOR]

Catestatin (CST), a 21-amino acids physiological peptide, has emerged as a key modulator of cardiovascular functions due to its anti-hypertensive and cardioprotective properties. However, the ramifications of the most common human variant of CST (viz., Gly364Ser) on cardiovascular pathophysiology remain partially understood. In this study, hypertension was induced in uninephrectomized rats by treatment with deoxycorticosterone-acetate and sodium chloride (DOCA-salt). The DOCA-salt-induced hypertensive (DSHR) animals were then intraperitoneally administered with either CST wild-type (CST-WT) or 364Ser variant (CST-Ser) peptide. CST-Ser was profoundly less effective than CST-WT in rescuing the elevated systolic blood pressure [from ∼211 mmHg to ∼176 mmHg, p < 0.0001 (CST-Ser) versus ∼116 mmHg, p < 0.0001 (CST-WT)] and heart rate [from ∼356 bpm to ∼314 bpm, p = 0.66 (CST-Ser) versus ∼276 bpm, p = 0.02 (CST-WT)]. CST-Ser also showed diminished effects in lowering diastolic blood pressure and mean arterial pressure in the DSHR animals. Furthermore, CST-Ser was inefficient/markedly less potent in rescuing the impaired contractile and diastolic function in DSHR animals [improvements in the contractility index by ∼22 s-1 (CST-Ser), p = 0.15 versus by ∼84 s-1 (CST-WT), p < 0.0001 and decrease in end-diastolic pressure by ∼4 mmHg (CST-Ser), p = 0.015 versus by ∼14 mmHg (CST-WT), p < 0.0001]. Moreover, CST-Ser exerted less potent anti-inflammatory effects on the DSHR hearts than CST-WT. These findings are in concordance with the elevated systolic/diastolic blood pressure observed in Ser variant carriers from various human populations. This study provides compelling evidence for the diminished anti-hypertensive and cardioprotective effects of the CST-Gly364Ser variant., (© 2024 The Author(s).)

Introduction: Recent studies showed that antimicrobial peptides have an essential role in the pathogenesis of acne vulgaris. This study aims to investigate serum catestatin levels in acne vulgaris patients and focuses on the change in serum levels after systemic isotretinoin therapy., Methods: This prospective study includes 101 acne vulgaris patients and 28 healthy controls. Serum catestatin levels were measured and compared between acne vulgaris and control group patients. Also, serum catestatin levels were measured again at the 24th week of isotretinoin therapy., Results: The serum catestatin levels in patients with acne vulgaris were statistically higher than in the control group ( p < 0.001). In addition, serum catestatin levels were associated with the severity of acne vulgaris. A significant decrease in serum catestatin levels was detected after 24 weeks of systemic isotretinoin treatment., Conclusion: Catestatin was found to be significantly higher in the serum of patients with acne vulgaris compared to the control group. Although, the demonstration that catestatin levels decrease with isotretinoin treatment may indicate that it may have an important role in the pathogenesis of acne and could be used as a biomarker, future studies are needed to establish the role of catestatin in the pathogenesis of acne vulgaris., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 S. Karger AG, Basel.)

The gut microbiota is in continuous interaction with the intestinal mucosa via metabolic, neuro-immunological, and neuroendocrine pathways. Disruption in levels of antimicrobial peptides produced by the enteroendocrine cells, such as catestatin, has been associated with changes in the gut microbiota and imbalance in intestinal homeostasis. However, whether the changes in the gut microbiota have a causational role in intestinal dyshomeostasis has remained elusive. To this end, we performed reciprocal fecal microbial transplantation in wild-type mice and mice with a knockout in the catestatin coding region of the chromogranin-A gene (CST-KO mice). Combined microbiota phylogenetic profiling, RNA sequencing, and transmission electron microscopy were employed. Fecal microbiota transplantation from mice deficient in catestatin (CST-KO) to microbiota-depleted wild-type mice induced transcriptional and physiological features characteristic of a distorted colon in the recipient animals, including impairment in tight junctions, as well as an increased collagen area fraction indicating colonic fibrosis. In contrast, fecal microbiota transplantation from wild-type mice to microbiota-depleted CST-KO mice reduced collagen fibrotic area, restored disrupted tight junction morphology, and altered fatty acid metabolism in recipient CST-KO mice. This study provides a comprehensive overview of the murine metabolic- and immune-related cellular pathways and processes that are co-mediated by the fecal microbiota transplantation and supports a prominent role for the gut microbiota in the colonic distortion associated with the lack of catestatin in mice. Overall, the data show that the gut microbiota may play a causal role in the development of features of intestinal inflammation and metabolic disorders, known to be associated with altered levels of catestatin and may, thus, provide a tractable target in the treatment and prevention of these disorders.

AimsAging is associated with the development of insulin resistance and hypertension which may stem from inflammation induced by accumulation of toxic bacterial DNA crossing the gut barrier. The aim of this study was to identify factors counter-regulating these processes. Taking advantage of the Chromogranin A (CgA) knockout (CgA-KO) mouse as a model for healthy aging, we have identified Vsig4 (V-set and immunoglobulin domain containing 4) as the critical checkpoint gene in offsetting age-associated hypertension and diabetes.Methods and ResultsThe CgA-KO mice display two opposite aging phenotypes: hypertension but heightened insulin sensitivity at young age, whereas the blood pressure normalizes at older age and insulin sensitivity further improves. In comparison, aging WT mice gradually lost glucose tolerance and insulin sensitivity and developed hypertension. The gut barrier, compromised in aging WT mice, was preserved in CgA KO mice leading to major 35-fold protection against bacterial DNA-induced inflammation. Similarly, RNA sequencing showed increased expression of the Vsig4 gene (which removes bacterial DNA) in the liver of 2-yr-old CgA-KO mice, which may account for the very low accumulation of microbial DNA in the heart. The reversal of hypertension in aging CgA-KO mice likely stems from (i) low accumulation of microbial DNA, (ii) decreased spillover of norepinephrine in the heart and kidneys, and (iii) reduced inflammation.ConclusionWe conclude that healthy aging relies on protection from bacterial DNA and the consequent low inflammation afforded by CgA-KO. Vsig4 also plays a crucial role in “healthy aging” by counteracting age-associated insulin resistance and hypertension.

Life-threatening diseases challenge immunity with a release of chromogranins. This report focuses on Chromogranin A (CGA) and some of its derived peptides in critically ill patients, with attention paid to their potential to become biomarkers of severity and actors of defense. First, we studied whether circulating CGA may be a biomarker of outcome in non-selected critically ill patients: CGA concentrations were reliably associated with short-term death, systemic inflammation, and multiple organ failure. Additionally, when studying Vasostatin-I, the major N-terminal fragment of CGA, we noted its reliable prognostic value as early as admission if associated with age and lactate. In trauma patients, CGA concentrations heralded the occurrence of care-related infections. This was associated with an in vitro inhibitor impact of Chromofungin on both NF-kappa B- and API-transcriptional activities. Secondly, in life-threatening disease-induced oxidative stress, the multimerization of Vasostatin-I occurs with the loss of its anti-microbial properties ex vivo. In vivo, a 4%-concentration of non-oxidized albumin infusion reversed multimerization with a decrease in care-related infections. Finally, in vitro Catestatin impacted the polymorphonuclear cells-Ca++-dependent, calmodulin–regulated iPLA2 pathway by releasing immunity-related proteins. Furthermore, human Cateslytin, the active domain of Catestatin, helped destroy S. aureus: this prompted the creation of synthetic D-stereoisomer of CGA-derived peptides against superbugs for the protection of implanted devices. In conclusion, CGA consideration in the critically ill is only starting, but it offers interesting perspectives for improved outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Neuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity. Patients & Methods: Admission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves). Results: Among COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or COVID-ICU+ patients (n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, p<0.03), with no difference between COVID+ and COVID-ICU+. There was no difference between groups in either CgA or CST/CgA ratios, but these parameters were lower in healthy controls (p<0.01). CST did not correlate with either hypoxia- or usual inflammation-related parameters. In-hospital mortality was similar whether COVID+ or not, but COVID+ had longer oxygen support and more complications (p<0.03). CST concentrations and the CST/CgA ratio were associated with in-hospital mortality (p<0.01) in COVID+, whereas CgA was not. CgA correlated with care-related infections (p<0.001). Conclusion: Respiratory COVID patients release significant amounts of CST in the plasma making this protein widely available for the neural regulation of immunity. If confirmed prospectively, plasma CST will reliably help in predicting in-hospital mortality, whereas CgA will facilitate the detection of patients prone to care-related infections. [ABSTRACT FROM AUTHOR]

Accumulating data suggests that catestatin, an eclectic neuroendocrine peptide, is involved in the pathophysiology of primary hypertension (PH). Nevertheless, clinical studies concerning its role in PH are still scarce. Therefore, in the present study, we aimed to explore an association between serum catestatin levels, ambulatory blood pressure (BP) and arterial stiffness in patients with PH and healthy controls. In this single-center study, 72 patients aged 40–70 diagnosed with PH, and 72 healthy controls were included. In patients with PH, serum catestatin concentrations were significantly higher in comparison to the healthy controls (29.70 (19.33–49.48) ng/mL vs. 5.83 (4.21–8.29) ng/mL, p < 0.001). Untreated patients had significantly higher serum catestatin than patients treated with antihypertensive drugs (41.61 (22.85–63.83) ng/mL vs. 24.77 (16.41–40.21) ng/mL, p = 0.005). Multiple linear regression analysis showed that serum catestatin levels retained a significant association with mean arterial pressure (β ± standard error, 0.8123 ± 0.3037, p < 0.009) after model adjustments for age, sex and body mass index. Finally, catestatin levels positively correlated with pulse wave velocity (r = 0.496, p < 0.001) and central augmentation index (r = 0.441, p < 0.001), but not with peripheral resistance. In summary, increased serum catestatin concentration in PH, predominantly in the untreated subgroup, and its association with ambulatory BP and arterial stiffness address the role of this peptide in PH. [ABSTRACT FROM AUTHOR]

Catestatin is a pleiotropic peptide with a wide range of immunomodulatory effects. Considering that patients with a severe COVID-19 infection have a major immunological dysregulation, the aim of this study was to evaluate catestatin levels in patients with COVID-19 treated in the intensive care unit (ICU) and to compare them between the fatal and non-fatal outcomes. The study included 152 patients with severe COVID-19, out of which 105 had a non-fatal outcome and 47 had a fatal outcome. Serum catestatin levels were estimated by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit. The results show that catestatin levels were significantly lower in the fatal group compared to the non-fatal group (16.6 ± 7.8 vs. 23.2 ± 9.2 ng/mL; p < 0.001). Furthermore, there was a significant positive correlation between serum catestatin levels and vitamin D levels (r = 0.338; p < 0.001) while there was also a significant positive correlation between serum catestatin levels and growth differentiation factor-15 (GDF-15) levels (r = −0.345; p < 0.001). Furthermore, multivariate logistic regression showed that catestatin, GDF-15 and leukocyte count were significant predictors for COVID-19 survival. These findings imply that catestatin could be playing a major immunomodulatory role in the complex pathophysiology of the COVID-19 infection and that serum catestatin could also be a predictor of a poor COVID-19 outcome. [ABSTRACT FROM AUTHOR]

Increased levels of the anti‐inflammatory peptide Catestatin (CST), a cleavage product of the pro‐hormone chromogranin A, correlate with less severe outcomes in hypertension, colitis, and diabetes. However, it is unknown how CST reduces the infiltration of monocytes and macrophages (Mϕs) in inflamed tissues. Here, it is reported that CST blocks leukocyte migration toward inflammatory chemokines. By in vitro and in vivo migration assays, it is shown that although CST itself is chemotactic, it blocks migration of monocytes and neutrophils to inflammatory attracting factor CC‐chemokine ligand 2 (CCL2) and C‐X‐C motif chemokine ligand 2 (CXCL2). Moreover, it directs CX3CR1+ Mϕs away from pancreatic islets. These findings suggest that the anti‐inflammatory actions of CST are partly caused by its regulation of chemotaxis. [ABSTRACT FROM AUTHOR]

Abstract Background Although preeclampsia has long been recognized as a condition affecting late pregnancy, little is known of its pathogenesis or treatment. The placenta releases a number of hormones and molecules that influence the course of pregnancy, one of which is chromogranin A, a soluble protein secreted mainly from the chromaffin cells of the adrenal medulla. Its role in pregnancy and pregnancy-related disorders remains unclear. Therefore, the main aim of the proposed study is to determine whether chromogranin A is related with the occurrence of preeclampsia. Methods Placental samples were collected from 102 preeclamptic patients and 103 healthy controls, and Chromogranin A gene (CHGA) expression was measured using real-time RT-PCR, The RT-PCR results were verified on the protein level using ELISA. The normal distribution of the data was tested using the Shapiro-Wilk test. The clinical and personal characteristics of the groups were compared using the Student’s t-test for normally-distributed data, and the χ2 test for categorical variables. The Mann-Whitney U test was used for non-normally distributed data. As the log- transformation was not suitable for the given outcomes, the Box- Cox Transformation was used to normalize data from ELISA tests and CHGA expression. Values of P

Abstract Objective Our aim was to analyse the chromogranin A-derived peptides vasostatin and catestatin in serum from wild boar (Sus scrofa) captured in a corral trap. Acute capture-related stress quickly leads to a release of adrenalin and noradrenalin, but these hormones have a short half-life in blood and are difficult to measure. Chromogranin A (CgA), a glycoprotein which is co-released with noradrenalin and adrenalin, is relatively stable in circulation and the CgA-derived peptides catestatin and vasostatin have been measured in domestic species, but not yet in wildlife. Results Vasostatin and catestatin could be measured and the median (range) serum concentrations were 0.91 (0.54–2.86) and 0.65 (0.35–2.62) nmol/L, respectively. We conclude that the CgA-derived peptides vasostatin and catestatin can be measured in wild boar serum and may thus be useful as biomarkers of psychophysical stress.

Chromogranin A (CgA) is a prohormone and a granulogenic factor that regulates secretory pathways in neuroendocrine tissues. In β-cells of the endocrine pancreas, CgA is a major cargo in insulin secretory vesicles. The impact of CgA deficiency on the formation and exocytosis of insulin vesicles is yet to be investigated. In addition, no literature exists on the impact of CgA on mitochondrial function in β-cells. Using three different antibodies, we demonstrate that CgA is processed to vasostatin- and catestatin-containing fragments in pancreatic islet cells. CgA deficiency in Chga-KO islets leads to compensatory overexpression of chromogranin B, secretogranin II, SNARE proteins and insulin genes, as well as increased insulin protein content. Ultrastructural studies of pancreatic islets revealed that Chga-KO β-cells contain fewer immature secretory granules than wild-type (WT) control but increased numbers of mature secretory granules and plasma membrane-docked vesicles. Compared to WT control, CgA-deficient β-cells exhibited increases in mitochondrial volume, numerical densities and fusion, as well as increased expression of nuclear encoded genes (Ndufa9, Ndufs8, Cyc1 and Atp5o). These changes in secretory vesicles and the mitochondria likely contribute to the increased glucose-stimulated insulin secretion observed in Chga-KO mice. We conclude that CgA is an important regulator for coordination of mitochondrial dynamics, secretory vesicular quanta and GSIS for optimal secretory functioning of β-cells, suggesting a strong, CgA-dependent positive link between mitochondrial fusion and GSIS.

IntroductionNeuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity.Patients & MethodsAdmission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves).ResultsAmong COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or (COVID-ICU+, patients n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, p

The rapid increase in drug-resistant and multidrug-resistant infections poses a serious challenge to antimicrobial therapies, and has created a global health crisis. Since antimicrobial peptides (AMPs) have escaped bacterial resistance throughout evolution, AMPs are a category of potential alternatives for antibiotic-resistant “superbugs”. The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352–372; bCgA344–364) was initially identified in 1997 as an acute nicotinic-cholinergic antagonist. Subsequently, CST was established as a pleiotropic hormone. In 2005, it was reported that N-terminal 15 amino acids of bovine CST (bCST1–15 aka cateslytin) exert antibacterial, antifungal, and antiyeast effects without showing any hemolytic effects. In 2017, D-bCST1–15 (where L-amino acids were changed to D-amino acids) was shown to exert very effective antimicrobial effects against various bacterial strains. Beyond antimicrobial effects, D-bCST1–15 potentiated (additive/synergistic) antibacterial effects of cefotaxime, amoxicillin, and methicillin. Furthermore, D-bCST1–15 neither triggered bacterial resistance nor elicited cytokine release. The present review will highlight the antimicrobial effects of CST, bCST1–15 (aka cateslytin), D-bCST1–15, and human variants of CST (Gly364Ser-CST and Pro370Leu-CST); evolutionary conservation of CST in mammals; and their potential as a therapy for antibiotic-resistant “superbugs”.

BACKGROUND: Previous studies have reported inconsistent findings regarding the association between catestatin and outcomes of acute myocardial infarction (AMI). This study aims to investigate the prognostic value of catestatin for long-term outcomes in patients with AMI. METHODS: One hundred and sixty-five patients with AMI were enrolled in this series. The plasma catestatin levels at baseline and clinical data were collected. All patients were followed up for four years to investigate whether there were major adverse cardiovascular events (MACEs), including cardiovascular death, recurrent AMI, rehospitalization for heart failure, and revascularization. RESULTS: There were 24 patients who had MACEs during the follow-up period. The MACEs group had significantly lower plasma catestatin levels (0.74±0.49 ng/mL vs. 1.10±0.79 ng/mL, P=0.033) and were older (59.0±11.4 years old vs. 53.2±12.8 years old, P=0.036). The rate of MACEs was significantly higher in the elderly group (£60 years old) than in the young group (<60 years old) (23.8% [15/63] vs. 8.8% [9/102], P=0.008). The catestatin level was significantly lower in the MACEs group than that in the non-MACEs group (0.76±0.50 ng/mL vs. 1.31±0.77 ng/mL, P=0.012), and catestatin was significantly associated with MACEs (Kaplan Meier, P=0.007) among the elderly group, but not in the young group (Kaplan Meier, P=0.893). In the Cox proportional hazards regression, high catestatin was one of the independent factors for predicting MACEs after adjustment for other risk factors (hazard ratio 0.19, 95% confidence interval 0.06-0.62, P=0.006) among elderly patients. CONCLUSIONS: Elderly AMI patients with lower plasma catestatin levels are more likely to develop MACEs. Catestatin may be a novel marker for the long-term prognosis of AMI, especially in elderly patients. [ABSTRACT FROM AUTHOR]

Aim: Defects in hepatic glycogen synthesis contribute to post‐prandial hyperglycaemia in type 2 diabetic patients. Chromogranin A (CgA) peptide Catestatin (CST: hCgA352‐372) improves glucose tolerance in insulin‐resistant mice. Here, we seek to determine whether CST induces hepatic glycogen synthesis. Methods: We determined liver glycogen, glucose‐6‐phosphate (G6P), uridine diphosphate glucose (UDPG) and glycogen synthase (GYS2) activities; plasma insulin, glucagon, noradrenaline and adrenaline levels in wild‐type (WT) as well as in CST knockout (CST‐KO) mice; glycogen synthesis and glycogenolysis in primary hepatocytes. We also analysed phosphorylation signals of insulin receptor (IR), insulin receptor substrate‐1 (IRS‐1), phosphatidylinositol‐dependent kinase‐1 (PDK‐1), GYS2, glycogen synthase kinase‐3β (GSK‐3β), AKT (a kinase in AKR mouse that produces Thymoma)/PKB (protein kinase B) and mammalian/mechanistic target of rapamycin (mTOR) by immunoblotting. Results: CST stimulated glycogen accumulation in fed and fasted liver and in primary hepatocytes. CST reduced plasma noradrenaline and adrenaline levels. CST also directly stimulated glycogenesis and inhibited noradrenaline and adrenaline‐induced glycogenolysis in hepatocytes. In addition, CST elevated the levels of UDPG and increased GYS2 activity. CST‐KO mice had decreased liver glycogen that was restored by treatment with CST, reinforcing the crucial role of CST in hepatic glycogenesis. CST improved insulin signals downstream of IR and IRS‐1 by enhancing phospho‐AKT signals through the stimulation of PDK‐1 and mTORC2 (mTOR Complex 2, rapamycin‐insensitive complex) activities. Conclusions: CST directly promotes the glycogenic pathway by (a) reducing glucose production, (b) increasing glycogen synthesis from UDPG, (c) reducing glycogenolysis and (d) enhancing downstream insulin signalling. [ABSTRACT FROM AUTHOR]

Catestatin is a multifunctional peptide that is involved in the regulation of the cardiovascular and immune systems as well as metabolic homeostatis. It mitigates detrimental, excessive activity of the sympathetic nervous system by inhibiting catecholamine secretion. Based on in vitro and in vivo studies, catestatin was shown to reduce adipose tissue, inhibit inflammatory response, prevent macrophage-driven atherosclerosis, and regulate cytokine production and release. Clinical studies indicate that catestatin may influence the processes leading to hypertension, affect the course of coronary artery diseases and heart failure. This review presents up-to-date research on catestatin with a particular emphasis on cardiovascular diseases based on a literature search.

The activation of glial cells and its possible mechanism play an extremely important role in understanding the pathophysiological process of some clinical diseases, and catestatin (CST) is involved in regulating this activation. In this project, we found that CST could enhance the activation of satellite glial cells (SGCs) and microglial cells and that the expression of P2X4 was increased; the co-expression of the P2X4 receptor with glial fibrillary acidic protein (GFAP) and the P2X4 receptor with CD11b was also increased significantly in glial cells of the ATP + CST group, and TNF-α and IL-1β also showed a rising trend; the expression of phosphorylated ERK1/2 was also increased in the ATP + CST group. In summary, we conclude that CST could enhance ATP-induced activation of SGCs and microglial cells mediated by the P2X4 receptor and that the ERK1/2 signaling pathway may be involved in this activation process. [ABSTRACT FROM AUTHOR]

Abstract Aims Soluble suppression of tumourigenicity 2 (sST2) and catestatin (CST) reflect myocardial fibrosis and sympathetic overactivity during the acute worsening of heart failure (AWHF). We aimed to determine serum levels and associations of sST2 and CST with in‐hospital death as well as the association between sST2 and CST among AWHF patients. Methods and results A total of 96 AWHF patients were consecutively enrolled, while levels of sST2 and CST were determined and compared between non‐survivors and survivors. Predictive values of sST2 and CST for in‐hospital death were determined by the penalized multivariable Firth logistic regression. The diagnostic ability of sST2 and CST for in‐hospital death was assessed by the receiver operating characteristic analysis and examined with respect to the N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin I, and C‐reactive protein. The in‐hospital death rate was 6.25%. Serum sST2 and CST levels were significantly higher among non‐survivors than survivors [146.6 (inter‐quartile range, IQR 65.9–156.2) vs. 35.3 (IQR 20.6–64.4) ng/mL, P