Chromogranin B in Heart Failure

Abstract

Background-Chromogranin B (CgB) is a member of the granin protein family. Because CgB is often colocalized with chromogranin A (CgA), a recently discovered cardiac biomarker, we hypothesized that CgB is regulated during heart failure (HF) development. Methods and Results-CgB regulation was investigated in patients with chronic HF and in a post-myocardial infarction HF mouse model. Animals were phenotypically characterized by echocardiography and euthanized 1 week after myocardial infarction. CgB mRNA levels were 5. Key Words: heart failure Ⅲ molecular biology Ⅲ biological markers Ⅲ chromogranin B A dvances in treatment of acute coronary syndromes have reduced short-term mortality following acute myocardial infarction (MI), but at the cost of a higher incidence of post-MI heart failure (HF). 1 Improved pathophysiological understanding of HF and better tools for risk prediction and diagnostic purposes are therefore needed. 2 The cardiac biomarkers used routinely in clinical practice today are proteins specific to the diseased myocardium, either released during cell necrosis (cardiac specific troponins) 3 or secreted secondary to cardiomyocyte strain (B-type natriuretic peptide, BNP). 4 However, there is still a need for markers reflecting other pathophysiological processes in heart disease. 5 Thus, identifying new proteins regulated in the failing myocardium may potentially improve both the understanding of HF development and lead to the discovery of novel cardiac biomarkers. Clinical Perspective on p 511Chromogranin B (CgB) is a 50-kDa protein belonging to a group of acidic proteins called the granin protein family. 6 The most extensively studied and well-known member of the granin family is chromogranin A (CgA), a protein currently used clinically as a biomarker in patients with neuroendocrine tumors. 7 Recently, CgA has been shown to increase with the severity of HF 8 and to be an independent predictor of mortality in patients with acute coronary syndrome. 9 -11 Moreover, increased CgA production has been demonstrated in cardiomyocytes of the failing myocardium. 12 However, a confounding factor possibly reducing CgA's merit as a cardiac biomarker is the increase in CgA levels seen with the use of proton pump inhibitors (PPIs). 13 In contrast, CgB Methods Mouse Model of HFA permanent ligation of the left main coronary artery were performed in mice in the HF group, whereas sham-operated (sham) animals underwent the same procedure except ligation of the coronary artery. 16 Echocardiographic examination was performed 1 week after the primary operation. The criteria for including animals in the HF group have previously been validated. 17

Secretogranin II; a Protein Increased in the Myocardium and Circulation in Heart Failure with Cardioprotective Properties

“…As previously reported for chromogranins [6], [17], SgII immunoreactivity was evident in cardiomyocytes, however, we also found SgII immunoreactivity in endothelial cells, fibroblasts, and other infiltrative cells of the border zone and the infarcted area (Figure 2B). The production of SgII in several cell types of the myocardium was validated by demonstrating similar SgII mRNA levels in fractions of cardiomyocytes, endothelial cells, and non-cardiomyocyte, non-endothelial cells (Figure 2C).…”

“…As evaluated by receiver operating analysis, circulating levels of SgII were more closely regulated in HF than both CgA (AUC = 0.84 for SgII vs. AUC = 0.57 for CgA, p = 0.001) and CgB levels (AUC = 0.68 for CgB, p = 0.03 vs. SgII). Use of a proton pump inhibitor (PPI), a medication known to increase circulating CgA levels [6], did not increase SgII levels as levels in patients using PPI (n = 8) were similar to SgII levels in the other HF patients: 0.16 (Q1–3 0.13–0.19) vs. 0.16 (0.14–0.18) nmol/L, respectively, p = 0.68).…”

“…Two other members of the granin protein family, chromogranin (Cg) A and B have been found increased in HF [4]–[6], and may represent novel cardiac biomarkers [4]–[9]. In addition, chromogranins may affect myocardial function in HF [10], [11].…”

From integrative genomics to systems genetics in the rat to link genotypes to phenotypes

“…Overall, this study illustrated that CpG methylation levels are under genetic control, providing a framework for the study of the molecular mechanisms underlying these processes, while also contributing to the understanding of the interrelation between the regulation of CpG methylation and pathophysiological cardiac phenotypes and biomarkers in the rat (Johnson et al, 2014). For instance, the team reported significant correlation between a locus-specific CpG methylation change in cardiac tissue and levels of serum chromogranin B, which is a correlate of sympathetic nervous system overactivity and has been proposed as a biomarker for heart failure (Røsjø et al, 2010). …”

Chromogranin B in Calpain-Mediated Hypertrophic Signaling—The Chicken, the Egg, or Even Both…?

“…6 Carrying forward the research on CGB in HF, these authors found increased circulating plasma CGB levels in HF patients that correlate with HF disease severity assessed by New York Heart Association (NYHA) functional class. In this context, CGB might not only become a novel target for specific therapeutic interventions but may as well aid in diagnosis and treatment of HF patients in its function as cardiac biomarker.…”