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: mChga364–384) 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 (hCHGA352–372) 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

Catestatin in heart and brain

Chromogranin A (CgA) and its processed, bioactive peptides are known effectors numerous biological pathways. Initially, CgA was studied as an important prohormone peptide of the chromaffin cells of the adrenal gland. Previous studies have shown CgA's necessity in the exocytosis and the release of peptides stored within dense -core secretory granules. Catestatin is a product of CgA processing and serves as a major inhibitor of CgA by antagonizing CgA's effects. This thesis investigated the expression of CgA and catestatin in tissues outside the adrenal gland. We were particularly interested in the tissues outside the adrenal medulla that incur collateral damage as a result of increased sympathetic tone. Specifically, we investigated the processing and expression of chromogranin A into its inhibitory peptide, catestatin in the heart and brain. We found not only a differential processing pattern between the adrenal, heart, and brain tissue, but also an age-dependent processing patter

Catestatin in heart and brain

Chromogranin A (CgA) and its processed, bioactive peptides are known effectors numerous biological pathways. Initially, CgA was studied as an important prohormone peptide of the chromaffin cells of the adrenal gland. Previous studies have shown CgA's necessity in the exocytosis and the release of peptides stored within dense -core secretory granules. Catestatin is a product of CgA processing and serves as a major inhibitor of CgA by antagonizing CgA's effects. This thesis investigated the expression of CgA and catestatin in tissues outside the adrenal gland. We were particularly interested in the tissues outside the adrenal medulla that incur collateral damage as a result of increased sympathetic tone. Specifically, we investigated the processing and expression of chromogranin A into its inhibitory peptide, catestatin in the heart and brain. We found not only a differential processing pattern between the adrenal, heart, and brain tissue, but also an age-dependent processing patter

Long-term clinical outcome and performance of transcatheter aortic valve replacement with a self-expandable bioprosthesis

In the last decade, transcatheter aortic valve (TAV) replacement determined a paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Data on long-term TAV performance are still limited. We sought to evaluate the clinical and haemodynamic outcomes of the CoreValve self-expandable valve up to 8-year follow-up (FU)