Chromogranin/secretogranin proteins in murine heart: myocardial production of chromogranin A fragment catestatin (Chga364-384)

In the heart, the secretory granules containing the atrial natriuretic peptides (ANP) and B-type myocardial natriuretic peptide (BNP) provide the basis for the endocrine function of this organ. We sought to determine whether atrial and myocardial secretory granules contain chromogranin/secretogranin proteins including chromogranin A (CHGA/Chga), chromogranin B (CHGB/Chgb) and secretogranin II (SCG2/Scg2). Deconvolution microscopy on immunolabeled proteins revealed the presence of Chga, Chgb, and Scg2 in murine cardiac secretory granules. The presence of low plasma catestatin (CST: mChga(364-384)) in older mice indicates diminished processing of Chga to CST with advancement of age, which is comparable to that found in humans. We have previously shown that CST (hCHGA(352-372)) exerts potent cardio-suppressive effects on frog and rat heart, but the source of CST for such action has remained elusive. In the present study, we found CST-related peptides in cardiomyocytes and in heart, which establishes an autocrine/paracrine function of CST in cardiac tissue. We conclude that cardiac secretory granules contain Chga, Chgb and Scg2 and that Chga is processed to CST in murine heart.