Glycosylated Chromogranin A: Potential Role in the Pathogenesis of Heart Failure
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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.
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.
KeywordsChromogranin A Glycosylation Secretoneurin Cardiovascular disease Heart failure
Work by the authors relating to granin proteins in cardiovascular disease have been funded by the Research Council of Norway, South-Eastern Regional Health Authority, Akershus University Hospital, Norwegian Health Association, the Anders Jahre Trust, Center for Heart Failure Research, University of Oslo, South-Eastern Norway Regional Health Authority, K.G. Jebsen Family Foundation, the Raagholt Trust, the Blix Trust, and the Odd Fellow Foundation.
Compliance with Ethical Standards
Conflicts of Interest
Anett H. Ottesen has received personal fees from CardiNor AS. TO has received research grants via Akershus University Hospital from Abbott Diagnostics, Roche Diagnostics, Singulex and AstraZeneca, and personal fees from Roche Diagnostics, Abbott Diagnostics, Bayer, Novartis, and CardiNor AS. HR has received personal fees from Novartis and CardiNor AS and research grants from Thermo Fisher BRAHMS, EuroDiagnostica, and Biomedica.
Helge Røsjø, Geir Christensen, and Torbjørn Omland are partners in a patent filed by the University of Oslo regarding the use of secretoneurin as a biomarker in patients with cardiovascular disease and patients with critical illness. HR, GC, and TO also have financial interests in CardiNor AS, which holds the license to commercialize secretoneurin.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted in bold and as: • Of importance
- 1.Ponikowski P, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail, 2016. 2016;18(8):891–975.CrossRefGoogle Scholar
- 51.• Ottesen AH, et al. Glycosylated chromogranin A in heart failure: implications for processing and cardiomyocyte calcium homeostasis. Circ Heart Fail. 2017. 10(2). First study to report myocardial CgA hyperglycosylation in heart failure and that this may influence disease progression Google Scholar
- 53.• Ceconi C, et al. Chromogranin A in heart failure; a novel neurohumoral factor and a predictor for mortality. Eur Heart J. 2002;23(12):967–74. First study to demonstrate increased circulating CgA concentrations in parallel with heart failure severity and the potential of CgA as a cardiac biomarker PubMedCrossRefGoogle Scholar
- 62.Myhre PL, et al. Circulating chromogranin B levels in patients with acute respiratory failure: data from the FINNALI Study. Biomarkers. 2017: 1–7.Google Scholar
- 77.Imbrogno S, et al. The catecholamine release-inhibitory peptide catestatin (chromogranin A344–363) modulates myocardial function in fish. J Exp Biol. 2010;213(Pt 21):3636–43.Google Scholar
- 90.Filice, E., et al., Chromofungin, CgA47-66-derived peptide, produces basal cardiac effects and postconditioning cardioprotective action during ischemia/reperfusion injury. Peptides, 2015. 71: p. 40-8.Google Scholar