Glycosylated Chromogranin A: Potential Role in the Pathogenesis of Heart Failure

Abstract

Chromogranin A is the most studied member of the granin protein family, and shorter, functionally active peptide fragments of chromogranin A exert protective effects on myocardial cell death, ischemia-reperfusion injury, and cardiomyocyte Ca handling. Granin peptides have also been found to induce angiogenesis and vasculogenesis. Protein glycosylation is an important post-translational regulatory mechanism, and we recently found chromogranin A molecules to be hyperglycosylated in the failing myocardium. Chromogranin A hyperglycosylation impaired processing of full-length chromogranin A molecules into physiologically active chromogranin A peptides, and patients with acute heart failure and low rate of chromogranin A processing had increased mortality compared to other acute heart failure patients. Other studies have also demonstrated that circulating granin protein concentrations increase in parallel with heart failure disease stage. The granin protein family seems to influence heart failure pathophysiology, and chromogranin A hyperglycosylation could directly be implicated in heart failure disease progression.

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“…178 Synthesis also occurs in non-neuroendocrine cells, including the heart, liver, and kidneys. 29,188,189 Production in these organs seems to increase with pathology and as these cells attain a paracrine/endocrine phenotype; including cells in the myocardium, 190,191 the prostate, 192,193 and lungs. 194 Common to all granin proteins is a single-polypeptide chain of 180-700 amino acids connected to an N-terminal signal peptide that have multiple dibasic cleavage sites.…”

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