Anett H Ottesen1,2,3, Geir Christensen2,3, Torbjørn Omland1,2, Helge Røsjø4,5,6. 1. Division of Medicine, Akershus University Hospital, Sykehusveien 25, 1478, Lørenskog, Norway. 2. Center for Heart Failure Research, University of Oslo, Oslo, Norway. 3. Institute for Experimental Medical Research, Oslo University Hospital, Ullevål, Oslo, Norway. 4. Division of Medicine, Akershus University Hospital, Sykehusveien 25, 1478, Lørenskog, Norway. helge.rosjo@medisin.uio.no. 5. Center for Heart Failure Research, University of Oslo, Oslo, Norway. helge.rosjo@medisin.uio.no. 6. University Hospital Uppsala and Uppsala Clinical Research Center, Uppsala, Sweden. helge.rosjo@medisin.uio.no.
Abstract
PURPOSE OF REVIEW: Endocrine and paracrine factors influence the cardiovascular system and the heart by a number of different mechanisms. The chromogranin-secretogranin (granin) proteins seem to represent a new family of proteins that exerts both direct and indirect effects on cardiac and vascular functions. The granin proteins are produced in multiple tissues, including cardiac cells, and circulating granin protein concentrations provide incremental prognostic information to established risk indices in patients with myocardial dysfunction. In this review, we provide recent data for the granin proteins in relation with cardiovascular disease, and with a special focus on chromogranin A and heart failure. RECENT FINDINGS: 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 Ca2+ 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.
PURPOSE OF REVIEW: Endocrine and paracrine factors influence the cardiovascular system and the heart by a number of different mechanisms. The chromogranin-secretogranin (granin) proteins seem to represent a new family of proteins that exerts both direct and indirect effects on cardiac and vascular functions. The granin proteins are produced in multiple tissues, including cardiac cells, and circulating granin protein concentrations provide incremental prognostic information to established risk indices in patients with myocardial dysfunction. In this review, we provide recent data for the granin proteins in relation with cardiovascular disease, and with a special focus on chromogranin A and heart failure. RECENT FINDINGS: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 Ca2+ 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 failurepatients. 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.
Authors: Tommaso Angelone; Anna Maria Quintieri; Bhawanjit K Brar; Pauline T Limchaiyawat; Bruno Tota; Sushil K Mahata; Maria Carmela Cerra Journal: Endocrinology Date: 2008-06-05 Impact factor: 4.736