Catestatin Levels Research Articles

Circulating levels of catestatin are significantly higher in heart failure patients with ischemic vs. non-ischemic cardiomyopathy: the role of catestatin as a compensatory marker of neurohumoral activation

Circulating levels of catestatin are significantly higher in heart failure patients with ischemic vs. non-ischemic cardiomyopathy: the role of catestatin as a compensatory marker of neurohumoral activation

Catestatin serum levels are increased in male patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a complex sleep disorder associated with autonomic and sympathetic dysregulation. To the contrary, catestatin, an endogenous pleiotropic peptide cleaved from chromogranin A, is known for its inhibitory effects on catecholamine release and sympathetic activity. The aims of the study were to determine catestatin serum levels among male OSA patients compared to healthy control subjects and to explore associations of catestatin with anthropometric, polysomnographic, and lipid profile parameters. Seventy-eight male OSA patients aged 50.3 ± 8.8years and 51 age/sex/BMI-matched control subjects aged 50.4 ± 7.8years were enrolled in the study. Catestatin serum levels were determined by an enzyme-linked immunosorbent assay (ELISA). Catestatin serum levels were significantly higher among OSA patients compared to control subjects (2.9 ± 1.2 vs. 1.5 ± 1.1ng/mL, p < 0.001). Serum catestatin levels significantly correlated with apnea-hypopnea index (AHI) among non-obese OSA subjects (r = 0.466, p = 0.016; β = 0.448, p = 0.026), while in whole OSA population, catestatin levels significantly correlated with neck circumference (r = 0.318, p < 0.001; β = 0.384, p < 0.001) and high-density lipoprotein (HDL) cholesterol (r = - 0.320, p < 0.001; β = - 0.344, p < 0.001). In multivariate-adjusted regression model, serum catestatin was significant and independent predictor of OSA status (OR 4.98, 95% CI 2.17-11.47, p < 0.001). Catestatin serum levels are significantly increased in male OSA population and positively correlate with disease severity in non-obese patients. OSA status is independently predicted by catestatin levels; however, this finding is restricted to patients with moderate-to-severe disease. Further studies are necessary to elucidate the mechanistic role of catestatin in the complex pathophysiology of OSA.

CATESTATIN AS A NOVEL MARKER OF CARDIOVASCULAR RISK IN SYSTEMIC HYPERTENSION

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.

Catestatin Prevents Macrophage-Driven Atherosclerosis but Not Arterial Injury-Induced Neointimal Hyperplasia.

Catestatin, a catecholamine-release inhibitory peptide, has multiple cardiovascular activities. Conflicting results have been recently reported by increased or decreased plasma levels of catestatin in patients with coronary artery disease (CAD). However, there have been no previous reports regarding the effects of catestatin on arteriosclerosis. This study evaluated the vasoprotective effects of catestatin on human macrophages, human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) in vitro, and aortic atherosclerosis and wire injury-induced femoral artery neointimal hyperplasia in apolipoprotein E-deficient (ApoE-/-) mice fed with a high-cholesterol diet. Histological expression of catestatin in coronary artery lesions and its plasma level were compared between CAD and non-CAD patients. Catestatin was abundantly expressed in cultured human monocytes, macrophages, HASMCs and HUVECs. Catestatin significantly suppressed lipopolysaccharide-induced upregulation of tumour necrosis factor-α, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in HUVECs. Catestatin significantly suppressed inflammatory responses and oxidized low-density lipoprotein-induced foam cell formation associated with acyl-CoA:cholesterol acyltransferase-1 downregulation and ATP-binding cassette transporter A1 upregulation in human macrophages. Catestatin significantly suppressed migration, proliferation and collagen-1 expression without inducing apoptosis, and increased elastin and fibronectin expression in HASMCs. Administration of catestatin into ApoE-/- mice significantly retarded entire aortic atherosclerotic lesions with declined contents of macrophages, SMCs and collagen fibres in atheromatous plaques, but not the femoral artery injury-induced neointimal hyperplasia. In CAD patients, catestatin levels were significantly decreased in plasma but increased in coronary atheromatous plaques. This study provided the first evidence that catestatin could prevent macrophage-driven atherosclerosis, but not SMC-derived neointimal hyperplasia after vascular injury.

Catestatin-A Novel Predictor of Left Ventricular Remodeling After Acute Myocardial Infarction

Catestatin was discovered as a potent inhibitor of catecholamine secretion and plays important roles in the cardiovascular system. Our previous study demonstrates a close relationship between catestatin levels and prognosis of ST-elevation myocardial infarction (STEMI). Using the same population, the goal of this study is to investigate the ability of catestatin to predict left ventricular (LV) remodeling in STEMI patients. 72 patients and 30 controls were included. Catestatin was sampled after admission to the emergency room (ER), at day3 (D3), and day7 (D7) after STEMI. Echocardiography was performed at D3 and after 65 months for evaluation of LVEDD, EF, IVS, LVPW, E, A, E’, E/A, and E/E’. The changes of these parameters from D3 to 65 months were used to reflect the changes of ventricular structure and function. We found that plasma catestatin levels at D3 were highly correlated with the changes of LVEDD, EF, E, A, E’, E/A, as well as E/E’. Patients with higher catestatin levels developed worse ventricular function during the follow-up period. Single-point catestatin was effective to predict LVEDD change. And concurrently increasing catestatin and NT-proBNP levels predicted the highest risk of LV remodeling. This study suggests an important prognostic information of catestatin on LV remodeling.

Increased plasma level of catestatin might be associated with poor prognosis in hemodialysis patients

Cardiac complication is a major cause of death in hemodialysis patients. The aim of the study was to determine the relationship between plasma catestatin level and cardiac death in those people. A total of 330 maintenance hemodialysis patients were included. Blood samples were collected. Plasma catestatin level was detected by enzyme-linked immunosorbent assay. Fluid status of each patient was expressed by overhydration to total body weight ratio and daily diuresis. Each patient was followed-up for 36months, unless some of them died in the follow-up period. In the follow-up period, only one hemodialysis patient was lost, 29 patients were died of cardiovascular diseases, 28 patients were died of other diseases and remaining 272 patients survived. Logistic multivariate regression analysis revealed that patients with plasma catestatin level ≥1.9ng/ml were associated with increased cardiac death risk (RR 6.13, 95% CI 2.54, 18.45), and survival analysis also showed that cardiac death rate in patients with plasma catestatin level ≥1.9ng/ml was elevated than that in patients with plasma catestatin level <1.9ng/ml (P<0.001). In addition, overhydration to total body weight ratio and daily diuresis both had significant linear correlations with plasma catestatin level (r=0.502, P<0.001 and r=-0.338, P<0.001). Circulating catestatin concentration might be an independent cardiac prognostic indicator in hemodialysis patients. Fluid status might be involved in the prognostic forecasting process.

The predictive value of plasma catestatin for all-cause and cardiac deaths in chronic heart failure patients

Catestatin (CST) is a proteolytic fragment of Chromogranin A with a broad spectrum of activities in the cardiovascular system. The level of plasma CST increases in chronic heart failure patients, but its potential relationship to patient prognosis is unknown. In this study, we measured plasma CST levels in 202 chronic heart failure patients and followed them for a median of 52.5 months. The plasma CST level was higher in patients with all-cause death and cardiac death than in survivors. According to univariate COX regression, higher plasma CST levels predicted increased risk of all-cause and cardiac death. After adjustment for other confounding factors, plasma CST was an independent risk factor for both outcomes, and the hazard ratios (HRs) were 1.84 (95% CI: 1.02–3.32, p=0.042) and 2.41 (95% CI: 1.26–4.62, p=0.008) for all-cause death and cardiac death, respectively. The new risk-predictive model considering CST was superior to the previous model for both outcomes by ANOVA and likelihood ratio tests (p=0.040 and p=0.008, respectively). Concurrent increases in plasma BNP (B-type natriuretic peptide) and CST levels predicted the highest risk for both all-cause and cardiac deaths [HR=5.18 (95% CI: 1.94–13.87, p=0.001) and HR=9.19 (95% CI: 2.75–30.78, p<0.001), respectively]. Large-scale studies are needed to further assess the value of plasma CST in predicting heart failure prognosis.

Plasma Catestatin in Patients with Acute Coronary Syndrome

Objectives: To measure plasma catestatin levels in patients with acute coronary syndrome and investigate whether there is an association between catestatin levels and long-term outcome. Methods: Patients (n = 170) with suspected acute coronary syndrome who underwent emergency coronary angiography were enrolled, including 46 with acute ST-segment elevation myocardial infarction (STEMI), 89 with unstable angina pectoris (UAP), and 35 without coronary artery disease (CAD). All patients were followed for 2 years to measure the occurrence of major adverse cardiovascular events (MACEs), including death from a cardiovascular cause, recurrent acute myocardial infarction, or hospital admission for heart failure or revascularization. Results: On average, the plasma catestatin levels in patients with STEMI (0.80 ± 0.62 ng/ml) and UAP (0.99 ± 0.63 ng/ml) were significantly lower than the levels seen in the control group with no evidence of CAD (1.38 ± 0.98 ng/ml; p = 0.001). In multivariable linear regression, body mass index, presence of hypertension, and type of CAD were independently related to the plasma catestatin level. However, there were no significant differences in MACEs between patients with high and low levels of catestatin. Conclusions: The plasma catestatin levels in patients with STEMI and UAP were lower than the levels seen in patients without CAD.

Plasma Catestatin: A Useful Biomarker for Coronary Collateral Development with Chronic Myocardial Ischemia.

BackgroundsCatestatin is an endogenous multifunctional neuroendocrinepeptide. Recently, catestatin was discovered as a novel angiogenic cytokine. The study was to investigate the associations between endogenous catestatin and coronary collateral development among the patients with chronic myocardial ischemia.MethodsThirty-eight patients with coronary artery chronic total occlusions (CTO) (CTO group) and 38 patients with normal coronary arteries (normal group) were enrolled in the series. Among the patients with CTO, coronary collateral development was graded according to the Rentrop score method. Rentrop score 0–1 collateral development was regarded as poor collateral group and 2–3 collateral development was regarded as good collateral group. Plasma catestatin level and vascular endothelial growth factor (VEGF) were measured by ELISA kits.ResultsThe plasma catestatin levels in CTO group were significantly higher than that in normal group (1.97±1.01 vs 1.36±0.97ng/ml, p = 0.009). In the CTO group, the patients with good collateral development had significantly higher catestatin and VEGF levels than those with poor collateral development (2.36±0.73 vs 1.61±1.12 ng/ml, p = 0.018; 425.23±140.10 vs 238.48±101.00pg/mL, p<0.001). There is a positive correlation between plasma catestatin levels and Rentrop scores (r = 0.40, p = 0.013) among the patients with CTO. However, there is no correlations between plasma catestatin levels and VEGF (r = -0.06, p = 0.744). In the multiple linear regression models, plasma catestatin level was one of the independent factors of coronary collateral development after adjustment for confounders.ConclusionsPlasma catestatin was associated with coronary collateral developments. It may be a useful biomarker for coronary collateral development and potential target for therapeutic angiogenesis in patients with CTO.

PS157 The Relationship Between Heart Rate Recovery and the Levels of Catestatin After Acute Myocardial Infarction

PS157 The Relationship Between Heart Rate Recovery and the Levels of Catestatin After Acute Myocardial Infarction

Role of catestatin in 2K1C-induced renal hypertension in rats and the underlying mechanism

To investigate the roles of catestatin (CST) in 2-kidney-1 clip (2K1C)-induced renal hypertension in rats, and to explore the underlying mechanism. Thirty six male SD rats were randomly divided into Sham group (n=15) and Model group(n=21).The model group was performed by 2K1C operation. For 2K1C operation, the left renal arteries were narrowed by cotton thread. The Sham group was treated with the same condition as the 2K1C group except the renal artery was narrowed. Tail-cuff systemic blood pressure of rats was measured before and every weeks after 2K1C operation. Six weeks after 2K1C operation, a carotid artery catheter was inserted to measure blood pressure of rats under anesthesia. Then, the model group was randomly subdivided into 2K1C group (n=15) and 2K1C+CST group (n=6). The rats of 2K1C+CST group were intravenous given CST (80 μg/100 g) and the rats of Sham or 2K1C group were given normal saline. All rats were sacrificed after blood pressure was measured and blood was collected. Then, the left ventricular plus interventricular septum weight (LV+S) was weighted and the ratio of (LV+S)/body weight(BW) was calculated as the index of left ventricular hypertrophy. Norepinephrine (NE) contents in plasma were determined by high performance liquid chromatography(HPLC) and CST contents in plasma by ELISA. The nitrite/nitrate contents in the left ventricular tissue and plasma were measured by nitrate reduction method to represent nitric oxide (NO)contents.Expression levels of CST in the left ventricle, kidney, medulla oblongata and adrenal gland,as well as eNOS and iNOS, were tested by Western blot. ①The 2K1C group had higher tail-artery blood pressure(P<0.01) and were more marked presence of right ventricular hypertrophy than those of sham group (P<0.01). Compared with Sham group, plasma CST content in 2K1C group was decreased by 226% (P<0.01), while plasma NE content in 2K1C group was increased by 246% (P<0.01), expression levels of chromograminA(Chga) in medulla oblongata of 2K1C group were increased by 108%, in leftventricle and kidneywere decreased by 60% and 30%, respectively (P<0.05).the content of NO in left ventricular and plasmawere increased by 46% and 24% respectively. ②The carotid arterial blood pressure of 2K1C group markedly reduced after administration of CST.③Compared with 2K1C group, the content of NO in left ventricul and plasma of 2K1C+CST group were increased by 35% and 19% respectively(P<0.05). The expression of eNOS in left ventricular of 2K1C+CST group were also obviously increased. The CST expression of 2K1C-induced renal hypertension rats is reduced and the effects of exogenous CST lowering their blood pressure may be related to NO/NOS system.Therefore, we speculate CST could contribute to the pathogenesis and progression of renal hypertension.

GW26-e1569 Relationship between catestatin and heart rate recovery after acute myocardial infarction

To investigate the relationship between catestatin level and heart rate recovery in patients with acute myocardial infarction treated with direct emergency PCI. The population of our study comprised 80 consecutive patients with STEMI who were admitted to the ward of cardiology department in Peking

GW26-e4582 Plasma catestatin: a biomarker for ST segment elevation myocardial infarction and unstable angina pectoris?

The aim of this study was to investigate plasma catestatin levels among patients with acute STEMI or unstable angina pectoris (UAP), and to explore the associations between catestatin and the long-term outcome of STEMI and UAP. The study enrolled 46 acute STEMI patients and 89 UAP patients who

A counterview of 'An investigation of the false discovery rate and the misinterpretation of p-values' by Colquhoun (2014).

A counterview of 'An investigation of the false discovery rate and the misinterpretation of p-values' by Colquhoun (2014).

Correlation of plasma catestatin level and the prognosis of patients with acute myocardial infarction.

Catestatin is a peptide which is a potent inhibitor of catecholamine secretion and played essential functions in the cardiovascular system. Previous research found that dramatic changes of catestatin were associated with hemodynamics in acute myocardial infarction (AMI) during the first week after the AMI symptoms onset, but whether catestatin is also involved in the pathophysiological progression after AMI and then a predictor for outcomes is not clear. The aim of this study is to determine the correlation of plasma catestatin levels at different time points and the prognosis of AMI. 100 participants recruited were all patients with AMI, all of who received successful primary percutaneous coronary intervention (PCI) within 12h from the AMI symptom onset in our center; the concentrations of plasma catestatin were evaluated from blood samples of those 100 participants. Subsequent 65 months' follow-up was performed after discharging to evaluate cardiac adverse events and the association between catestatin levels and prognosis of AMI was examined. We confirmed the dramatic change of catestatin concentrations in the first week of AMI, and the levels of catestatin on D3 were much higher in adverse events group than those in non-adverse events group (p<0.0001), but the ratio of D7/D3 was significantly lower. In addition, the Kaplan-Meier analysis showed that the groups in which the levels on D3 were higher (p<0.0001) and the ratios of D7/D3 were lower (p<0.0001), patients trended to be more susceptive to adverse events after AMI. Furthermore, according to the analysis, we surmised catestatin level on D3 as an appropriate predictor for outcomes in patients with AMI with good specificity as well as sensitivity. All of the evidence confirmed that catestatin plays an important role in the progress of AMI, and may act as a promising target for prognostic prediction.

The relationship of plasma catestatin concentrations with metabolic and vascular parameters in untreated hypertensive patients: Influence on high-density lipoprotein cholesterol.

Objective:Catestatin has several cardiovascular actions, in addition to diminished sympatho-adrenal flow. Decreased plasma catestatin levels may reflect a predisposition for the development of hypertension and metabolic disorders. We planned to investigate the possible roles of catestatin in untreated hypertensive patients. As a secondary objective, we compared catestatin concentrations of healthy subjects with those of hypertensive patients in order to understand whether catestatin is increased reactively or diminished at onset.Methods:Our study was cross-sectional and observational. The patient group, comprising 109 consecutive untreated hypertensive patients without additional systemic or coronary heart disease, underwent evaluations of plasma catestatin, waist circumference, lipid parameters, left ventricular mass, carotid intima-media thickness, and flow-mediated dilation of the brachial artery. Additionally, we measured catestatin concentrations of 38 apparently healthy subjects without any disease using a commercial enzyme-linked immunosorbent assay kit.Results:We documented increased catestatin concentrations in previously untreated hypertensive patients compared to healthy controls (2.27±0.83 vs. 1.92±0.49 ng/mL, p=0.004). However, this association became insignificant after adjustments for age, gender, height, and weight. Within the patient group, catestatin levels were significantly higher in females. Among all study parameters, age, high-density lipoprotein cholesterol (HDL-C) correlated positively to plasma catestatin, whereas triglycerides, hemoglobin, and left ventricular mass correlated negatively to plasma catestatin. We could not detect an association between vascular parameters and catestatin. Catestatin levels were significantly elevated with increasing HDL-C (1.91±0.37, 2.26±0.79, and 3.1±1.23 ng/mL in patients with HDL-C <40, 40-60, and >60 mg/dL, respectively). Multiple linear regression analysis revealed age (beta: 0.201, p=0.041) and HDL-C (beta: 0.390, p<0.001) as independent correlates of plasma catestatin concentration. Additionally, male gender (beta:-0.330, p=0.001) and plasma catestatin (beta: 0.299, p=0.002) were significantly associated with HDL-C concentrations.Conclusion:We documented that plasma catestatin is an independent predictor of high-density lipoprotein cholesterol. In addition to antihypertensive effects, catestatin appears to be related to improved lipid and metabolic profiles. Coexistence of low catestatin levels with low HDL-C may provide a probable mechanism for the predictive value of low HDL-C for increased hypertension and cardiovascular events.

Usefulness of catestatin to predict malignant arrhythmia in patients with acute myocardial infarction

Catestatin (CST) displays potent vasodilatory effect and acts on lowering blood pressure in vivo. The clinical utility of CST in patients with acute myocardial infarction (AMI) has not been clearly delineated. The aim of this study was to investigate the predictive value of CST for the development of in-hospital malignant arrhythmia and other adverse cardiac events in patients with AMI. A total of 125 consecutive patients diagnosed with AMI were included. The clinical characteristics and previous history of the patients were collected. Malignant arrhythmia and other major adverse cardiac events (MACE) such as postinfarction angina pectoris or reinfarction and death were recorded during hospitalization. The levels of plasma CST, norepinephrine (NE) and amino-terminal pro-brain sodium peptides (NT-proBNP) were determined by sandwich ELISA. A multiple logistic regression model was used to predict the influence factors of malignant arrhythmia and other MACE during hospitalization of AMI patients. The results showed that the levels of plasma cystatin-C (CysC), high sensitivity C-reactive protein (hs-CRP), NE and NT-proBNP increased in a CST concentration dependent manner. The incidence of malignant arrhythmia significantly increased as the elevation of CST level (P<0.05). Age, CST and NT-proBNP were independent predictors for the MACE occurred during hospitalization. Increased blood glucose (≥6.1mmol/L) and CST were independent predictors for the complicated malignant arrhythmia of AMI patients. These data demonstrated that CST can be used as a new biological marker for prediction of malignant arrhythmia in patients with AMI.

Plasma levels and potential roles of catestatin in patients with coronary heart disease

Objectives. Catestatin (CST) is a new endogenous neuropeptide with a potent catecholamine release-inhibitory activity. This study was to investigate plasma CST levels in patients with coronary heart disease (CHD) and to determine the clinical significance of plasma CST in cardiovascular events. Methods. A total of 120 CHD patients and 30 age/sex-matched healthy subjects were enrolled. Plasma CST level was measured using enzyme-linked immunosorbent assay (ELISA) and norepinephrine (NE) level was measured using high-performance liquid chromatography (HPLC). Clinical and laboratory data during hospitalization were collected, and a follow-up of 1045 days was carried out. Results. Compared with controls, CHD patients had significantly higher plasma CST and NE levels on admission. ST segment elevation myocardial infarction (STEMI) patients had higher CST levels than angina pectoris patients had, but CST/NE ratios were unchanged among controls and different CHD subgroups. Plasma NE was the only independent factor associated with CST. As a dichotomous variable divided by the median value, plasma CST on admission was not associated with adverse cardiovascular events. Conclusions. Plasma CST level was positively correlated with that of NE and was elevated in parallel with that of NE in the different myocardial ischemia states. Plasma CST on admission was neither associated with adverse cardiac events nor was there any significant relationship between plasma CST and onset of new cardiovascular events. The pathophysiological role of CST in CHD needs further studies.

Plasma levels and diagnostic value of catestatin in patients with heart failure

Catestatin (CST) is an endogenous neuropeptide with multiple cardiovascular activities. The study is to investigate circulating CST levels in heart failure (HF) patients and to evaluate the role of CST as a biomarker for HF. Plasma CST concentrations were measured by enzyme-linked immunosorbent assay in 228 HF patients and 172 controls. Plasma CST gradually increased in patients from NYHA class I to class IV. No significant differences in CST were found among NYHA I, NYHA II patients and controls. Plasma CST in NYHA III and IV patients was higher compared to other groups. Plasma CST levels in HF patients after treatment were similar to admission, but still higher than controls. In a subgroup analysis among the patients with NYHA class III or IV, patients with ischemic etiology had significantly higher CST. Plasma CST levels were similar between patients with preserved and reduced ejection fraction. Multivariable analysis showed that NYHA classes, the etiology of HF (ischemic or not) and estimated glomerular filtration rate independently predicted plasma LogCST levels (P<0.05). The area under ROC for CST and BNP in moderate to severe HF diagnosis was 0.626 and 0.831, respectively, combining CST and BNP did not improve the accuracy.

Plasma catestatin level in patients with acute myocardial infarction and its correlation with ventricular remodelling

BackgroundThe evaluation of ventricular remodelling and functional recovery is essential in predicting the prognosis of patients with acute myocardial infarction (AMI).ObjectiveTo determine the plasma catestatin level in patients with AMI,...