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

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.

Summary

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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Acknowledgements

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.

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Correspondence to Helge Røsjø.

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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.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Pathophysiology: Neuroendocrine, Vascular, and Metabolic Factors

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Ottesen, A.H., Christensen, G., Omland, T. et al. Glycosylated Chromogranin A: Potential Role in the Pathogenesis of Heart Failure. Curr Heart Fail Rep 14, 478–488 (2017). https://doi.org/10.1007/s11897-017-0360-x

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Keywords

  • Chromogranin A
  • Glycosylation
  • Secretoneurin
  • Cardiovascular disease
  • Heart failure