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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.

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

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]

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.

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.

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

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.

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.

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”.

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.

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

The morbidity and mortality rates for acute myocardial infarction (AMI) have been growing rapidly in the recent years, causing a significant socio-economic damage. The cardiospecific biomarkers play an important role in the diagnosis and prediction of AMI. The purpose of this review is to summarize the information about the main existing cardiac biomarkers and their diagnostic and prognostic value for patients with AMI. The currently existing cardiac biomarkers of AMI may be divided into several groups: biomarkers of necrosis and ischemia of cardiomyocytes, neuroendocrine biomarkers, inflammatory biomarkers, as well as a number of new AMI biomarkers, the diagnostic value of which is still poorly understood in AMI. In the first part of the review, we discuss the diagnostic and prognostic value of the biomarkers of myocardial necrosis and ischemia (aspartate aminotransferase; creatine phosphokinase and its isoform MB; cardiac troponins; myoglobin; BB-isoform of glycogen phosphorylase; ischemia-modified albumin; cardiac protein binding fatty acids) and neuroendocrine biomarkers of AMI (natriuretic peptides; adrenomedulline; copeptin, catestatin; components of the renin-angiotensin-aldosterone system).

Abstract Background The protein chromogranin A (CgA) is stored and co-released with catecholamines from the stimulated adrenal glands. Increased plasma concentrations of CgA have been shown in people with heart disease. The aim of the study was to investigate whether plasma concentrations of the CgA-derived biologically active peptides catestatin and vasostatin were associated with the severity of myxomatous mitral valve disease (MMVD) in dogs and to assess potential associations between these blood variables and dog characteristics, echocardiographic variables, heart rate (HR), blood pressure (BP) and plasma N-terminal-proBNP (NT-proBNP) concentration. Sixty-seven privately owned dogs with or without MMVD were included. The dogs underwent physical examination, blood pressure measurement, blood sample collection, and echocardiographic examination. Plasma concentrations of catestatin and vasostatin were analyzed using radioimmunoassay. Results Catestatin concentration decreased with increasing left atrial and ventricular size (R2 ≤ 0.09, P ≤ 0.019), and increased with increasing systolic and diastolic blood pressures (R2 ≤ 0.08, P ≤ 0.038). Regression analyses showed no significant associations for vasostatin. No differences in plasma concentrations of catestatin or vasostatin were found between the disease severity groups used in the study. Conclusions In the present dog population, the catestatin concentration showed weak negative associations with left atrial and ventricular sizes, both of which are known to increase with increasing severity of MMVD. Furthermore, the catestatin concentration showed weak positive associations with blood pressure.

Obesity is characterized by a state of chronic, unresolved inflammation in insulin-targeted tissues. Obesity-induced inflammation causes accumulation of proinflammatory macrophages in adipose tissue and liver. Proinflammatory cytokines released from tissue macrophages inhibits insulin sensitivity. Obesity also leads to inflammation-induced endoplasmic reticulum (ER) stress and insulin resistance. In this scenario, based on the data (specifically patterns) generated by our in vivo experiments on both diet-induced obese (DIO) and normal chow diet (NCD) mice, we developed an in silico state space model to integrate ER stress and insulin signaling pathways. Computational results successfully followed the experimental results for both DIO and NCD conditions. Chromogranin A (CgA) peptide catestatin (CST: hCgA352-372) improves obesity-induced hepatic insulin resistance by reducing inflammation and inhibiting proinflammatory macrophage infiltration. We reasoned that the anti-inflammatory effects of CST would alleviate ER stress. CST decreased obesity-induced ER dilation in hepatocytes and macrophages. On application of Proportional-Integral-Derivative (PID) controllers on the in silico model, we checked whether the reduction of phosphorylated PERK resulting in attenuation of ER stress, resembling CST effect, could enhance insulin sensitivity. The simulation results clearly pointed out that CST not only decreased ER stress but also enhanced insulin sensitivity in mammalian cells. In vivo experiment validated the simulation results by depicting that CST caused decrease in phosphorylation of UPR signaling molecules and increased phosphorylation of insulin signaling molecules. Besides simulation results predicted that enhancement of AKT phosphorylation helps in both overcoming ER stress and achieving insulin sensitivity. These effects of CST were verified in hepatocyte culture model.

The autonomic nervous system is crucial in initiating and maintaining atrial fibrillation (AF). Catestatin is a multipurpose peptide that regulates cardiovascular systems and reduces harmful, excessive activity of the sympathetic nervous system by blocking the release of catecholamines. We aimed to determine whether serum catestatin concentrations are associated with AF severity, duration indices, and various clinical and laboratory indicators in these individuals to better define the clinical value of catestatin in patients with AF. The present single center study enrolled 73 participants with AF and 72 healthy age-matched controls. Serum catestatin concentrations were markedly higher in AF patients than controls (14.11 (10.21–26.02) ng/mL vs. 10.93 (5.70–20.01) ng/mL, p = 0.013). Furthermore, patients with a more severe form of AF had significantly higher serum catestatin (17.56 (12.80–40.35) vs. 10.98 (8.38–20.91) ng/mL, p = 0.001). Patients with higher CHA2DS2-VASc scores (17.58 (11.89–37.87) vs. 13.02 (8.47–22.75) ng/mL, p = 0.034) and higher NT-proBNP levels (17.58 (IQR 13.91–34.62) vs. 13.23 (IQR 9.04–22.61), p = 0.036) had significantly higher serum catestatin concentrations. Finally, AF duration correlated negatively with serum catestatin levels (r = −0.348, p = 0.003). The results of the present study implicate the promising role of catestatin in the intricate pathophysiology of AF, which should be explored in future research.

The current literature review covers the role of sympathetic nervous system activation (SNS) and the significance of a new biomarker catestatin (CST), which is a chromogranin A-derived peptide, for assessing prognosis of patients with heart failure (HF). This review details the works devoted to CST metabolism and its role in clinical conditions with excessive catecholamine production, including the ability to counterbalance the adverse effects of SNS on cardiovascular system. The paper also presents the central results of studies on HF patients and shows the correlation of the CST level with HF functional class and stage. In addition, particular attention is paid on the possibilities and potential benefits of assessing the CST in addition to conventional management of patients hospitalized due to acute decompensated heart failure.

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.

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.

Aim. To study the catestatin plasma level in patients with primary hypertension of different cardiovascular risk and to assess its relationship with heart rate variability (HRV) parameters.Material and methods. One hundred eighty men aged 30-50 years were divided into groups: group 1 (n=28) — hypertensive patients with medium risk of developing cardiovascular complications (CVC), group 2 (n=76) — hypertensive patients with high risk of CVC, group 3 (n=31) — hypertensive patients with very high risk of CVC. The control group consisted of healthy men with normal blood pressure (BP) (n=45). We determined plasma catestatin (ng/ml) and conducted Holter monitoring.Results. A pattern was found to reduce the concentration of catestatin with increasing risk of CVC in hypertensive patients, but there were no significant differences between the studied groups (p>0,05).We determined corrections between catestatin levels and echocardiography thickness of left ventricular posterior wall (r=-0,523; p=0,045) and interventricular septum (r=-0,523, p=0,045) in diastole in group 2; thickness of left ventricular posterior wall (r=0,258; p=0,035) and interventricular septum (r=0,254; p=0,038) in systole in group 3. In patients of group 2, direct correlations of catestatin levels and sympathicotonia LF/HF were revealed during the whole observation period (r=0,301; p=0,019) and during wakefulness (r=0,308; p=0,019); inverse correlations — with parameters of parasympathetic tone: nHF during the whole observation time (r=-0,318; p=0,013) and during wakefulness (r=-0,342; p=0,007), pNN50 in the afternoon (r=-0,270; p=0,037).Conclusion. A decrease in catestatin concentrations in hypertensive patients is associated with the progression of disease and an increase in cardiovascular risk. It is assumed that catestatin is involved in the formation of HRV in patients with primary hypertension.

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.

Background/Aims: Neuropathic pain (NPP) is the consequence of a number of central nervous system injuries or diseases. Previous studies have shown that NPP is mediated by P2X4 receptors that are expressed on satellite glial cells (SGCs) of dorsal root ganglia (DRG). Catestatin (CST), a neuroendocrine multifunctional peptide, may be involved in the pathogenesis of NPP. Here, we studied the mechanism through which CST affects NPP. Methods: We made rat models of chronic constriction injury (CCI) that simulate neuropathic pain. Rat behavioral changes were estimated by measuring the degree of hyperalgesia as assessed by the mechanical withdrawal threshold (MWT) and the thermal withdrawal latency (TWL). P2X4 mRNA expression was detected by quantitative real-time reverse transcription-polymerase chain reaction. P2X4 protein level and related signal pathways were assessed by western blot. Additionally, double-labeled immunofluorescence was employed to visualize the correspondence between the P2X4 receptor and glial fibrillary acidic protein. An enzyme-linked immunosorbent assay was performed to determine the concentration of CST and inflammatory factors. Results: CST led to lower MWT and TWL and increased P2X4 mRNA and protein expression on the SGCs of model rats. Further, CST upregulated the expression of phosphor-p38 and phosphor-ERK 1/2 on the SGCs of CCI rats. However, the expression level of phosphor-JNK and phosphor-p65 did not obviously change. Conclusion: Taken together, CST might boost NPP by enhancing the sensitivity of P2X4 receptors in the DRG of rats, which would provide us a novel perspective and research direction to explore new therapeutic targets for NPP.

Review of the key studies on antihypertensive, vasodilatatory, angiogenic and antiapoptotic action of catestatin — a peptide resulting from endogenic protease interaction with chromogranin А. Plasma levels of catestatin correlate negatively with the hypertension phenotype. Pathogenetic role is discussed for catestatin in development of essential hypertension and its possible influence as a marker of cardiovascular risk stratification.

Accounting for almost one-third of the global mortality, cardiovascular diseases (CVDs) represent a major global health issue. Emerging data suggest that most of the well-established mechanistic explanations regarding the cardiovascular pathophysiology are flawed, and cannot fully explain the progression and long-term effects of these diseases. On the other hand, dysregulation of the sympathetic nervous system (SNS) has emerged as an important player in the pathophysiology of CVDs. Even though upregulated SNS activity is an essential compensatory response to various stress conditions, in the long term, it becomes a major contributor to both cardiac dysfunction and vascular damage. Despite the fact that the importance of SNS hyperactivity in the setting of CVDs has been well-appreciated, its exact quantification and clinical application in either diagnostics or therapy of CVDs is still out of reach. Nevertheless, in recent years a number of novel laboratory biomarkers implicated in the pathophysiology of SNS activation have been explored. Specifically, in this review, we aimed to discuss the role of catestatin, a potent physiological inhibitor of catecholamine spillover that offers cardioprotective effects. Limited data indicate that catestatin could also be a reliable indirect marker of SNS activity and it is likely that high CST levels reflect advanced CV disease burden. Consequently, large-scale studies are required to validate these observations in the upcoming future.

Catestatin (CST) is a pleiotropic peptide involved in cardiovascular protection with its antihypertensive and angiogenic effects. Considering that patients with end-stage renal disease (ESRD) who are undergoing hemodialysis (HD) are associated with higher cardiovascular risk, the aim of this study was to investigate plasma CST levels in HD patients, compare them to healthy controls and evaluate possible CST associations with advanced glycation end products (AGEs) and laboratory, anthropometric and clinical parameters. The study included 91 patients on HD and 70 healthy controls. Plasma CST levels were determined by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit, while AGEs were determined using skin autofluorescence. Plasma CST levels were significantly higher in the HD group compared to the controls (32.85 ± 20.18 vs. 5.39 ± 1.24 ng/mL, p < 0.001) and there was a significant positive correlation between CST and AGEs (r = 0.492, p < 0.001). Furthermore, there was a significant positive correlation between plasma CST levels with both the Dialysis Malnutrition Score (r = 0.295, p = 0.004) and Malnutrition-Inflammation Score (r = 0.290, p = 0.005). These results suggest that CST could be playing a role in the complex pathophysiology of ESRD/HD and that it could affect the higher cardiovascular risk of patients on HD.

Recent advances in understanding the intracellular and intercellular features of adrenal chromatin cells as stress transducers are reviewed here, along with their implications for endocrine function in other tissues and organs participating in endocrine regulation in the mammalian organism.

It is increasingly clear that inflammatory diseases and cancers are influenced by cleavage products of the pro-hormone chromogranin A (CgA), such as the 21-amino acids long catestatin (CST). The goal of this review is to provide an overview of the anti-inflammatory effects of CST and its mechanism of action. We discuss evidence proving that CST and its precursor CgA are crucial for maintaining metabolic and immune homeostasis. CST could reduce inflammation in various mouse models for diabetes, colitis and atherosclerosis. In these mouse models, CST treatment resulted in less infiltration of immune cells in affected tissues, although in vitro monocyte migration was increased by CST. Both in vivo and in vitro, CST can shift macrophage differentiation from a pro- to an anti-inflammatory phenotype. Thus, the concept is emerging that CST plays a role in tissue homeostasis by regulating immune cell infiltration and macrophage differentiation. These findings warrant studying the effects of CST in humans and make it an interesting therapeutic target for treatment and/or diagnosis of various metabolic and immune diseases.

While there is growing awareness of a relationship between chromogranin-A (CHGA) and susceptibility to inflammatory conditions, the role of human catestatin [(hCTS); CHGA352–67] in the natural history of established inflammatory bowel disease is not known. Recently, using two different experimental models, we demonstrated that hCTS-treated mice develop less severe acute colitis. We have also shown the implication of the macrophages in this effect. The aims of this study were to determine (1) whether hCTS treatment could attenuate the reactivation of inflammation in adult mice with previously established chronic colitis; (2) whether this effect is mediated through macrophages or the gut microbiota. Quiescent colitis was induced in 7–8-week-old C57BL6 mice using four cycles (2–4%) of dextran sulfate sodium. hCTS (1.5 mg/kg/day) treatment or vehicle started 2 days before the last induction of colitis and continuing for 7 days. At sacrifice, macro- and microscopic scores were determined. Colonic pro-inflammatory cytokines [interleukin (IL)-6, IL-1β, and TNF- α], anti-inflammatory cytokines (IL-10, TGF- β), classically activated (M1) (iNOS, Mcp1), and alternatively activated (M2) (Ym1, Arg1) macrophages markers were studied using ELISA and/or RT-qPCR. In vitro, peritoneal macrophages isolated from naïve mice and treated with hCTS (10−5 M, 12 h) were exposed to either lipopolysaccharide (100 ng/ml, 12 h) to polarize M1 macrophages or to IL-4/IL-13 (20 ng/ml) to polarize M2 macrophages. M1/M2 macrophage markers along with cytokine gene expression were determined using RT-qPCR. Feces and mucosa-associated microbiota (MAM) samples were collected, and the V4 region of 16 s rRNA was sequenced. Micro- and macroscopic scores, colonic IL-6, IL-1β, TNF- α, and M1 macrophages markers were significantly decreased in the hCTS-treated group. Treatment did not have any effect on colonic IL-10, TGF-β, and M2 markers nor modified the bacterial richness, diversity, or the major phyla in colitic fecal and MAM samples. In vitro, pro-inflammatory cytokines levels, as well as their gene expression, were significantly reduced in hCTS-treated M1 macrophages. hCTS treatment did not affect M2 macrophage markers. These findings suggest that hCTS treatment attenuates the severity of inflammatory relapse through the modulation of the M1 macrophages and the release of pro-inflammatory cytokines.

Together with Chromogranin B and Secretogranins, Chromogranin A (CGA) is stored in secretory (chromaffin) granules of the diffuse neuroendocrine system and released with noradrenalin and adrenalin. Co-stored within the granule together with neuropeptideY, cardiac natriuretic peptide hormones, several prohormones and their proteolytic enzymes, CGA is a multifunctional protein and a major marker of the sympatho-adrenal neuroendocrine activity. Due to its partial processing to several biologically active peptides, CGA appears an important pro-hormone implicated in relevant modulatory actions on endocrine, cardiovascular, metabolic, and immune systems through both direct and indirect sympatho-adrenergic interactions. As a part of this scenario, we here illustrate the emerging role exerted by the full-length CGA and its three derived fragments, i.e. Vasostatin 1, catestatin and serpinin, in the control of circulatory homeostasis with particular emphasis on their cardio-vascular actions under both physiological and physio-pathological conditions. The Vasostatin 1- and catestatin-induced cardiodepressive influences are achieved through anti-beta-adrenergic-NO-cGMP signalling, while serpinin acts like beta1-adrenergic agonist through AD-cAMP-independent NO signalling. On the whole, these actions contribute to wide our knowledge regarding the sympatho-chromaffin control of the cardiovascular system and its highly integrated whip-brake networks.