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Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation.

Barallobre-Barreiro, J; Gupta, SK; Zoccarato, A; Kitazume-Taneike, R; Fava, M; Yin, X; Werner, T; Hirt, MN; Zampetaki, A; Viviano, A; et al. Barallobre-Barreiro, J; Gupta, SK; Zoccarato, A; Kitazume-Taneike, R; Fava, M; Yin, X; Werner, T; Hirt, MN; Zampetaki, A; Viviano, A; Chong, M; Bern, M; Kourliouros, A; Domenech, N; Willeit, P; Shah, AM; Jahangiri, M; Schaefer, L; Fischer, JW; Iozzo, RV; Viner, R; Thum, T; Heineke, J; Kichler, A; Otsu, K; Mayr, M (2016) Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation. Circulation, 134 (11). pp. 817-832. ISSN 1524-4539 https://doi.org/10.1161/CIRCULATIONAHA.115.016423
SGUL Authors: Jahangiri, Marjan

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Abstract

BACKGROUND: Myocardial fibrosis is a feature of many cardiac diseases. We used proteomics to profile glycoproteins in the human cardiac extracellular matrix (ECM). METHODS: Atrial specimens were analyzed by mass spectrometry after extraction of ECM proteins and enrichment for glycoproteins or glycopeptides. RESULTS: ECM-related glycoproteins were identified in left and right atrial appendages from the same patients. Several known glycosylation sites were confirmed. In addition, putative and novel glycosylation sites were detected. On enrichment for glycoproteins, peptides of the small leucine-rich proteoglycan decorin were identified consistently in the flowthrough. Of all ECM proteins identified, decorin was found to be the most fragmented. Within its protein core, 18 different cleavage sites were identified. In contrast, less cleavage was observed for biglycan, the most closely related proteoglycan. Decorin processing differed between human ventricles and atria and was altered in disease. The C-terminus of decorin, important for the interaction with connective tissue growth factor, was detected predominantly in ventricles in comparison with atria. In contrast, atrial appendages from patients in persistent atrial fibrillation had greater levels of full-length decorin but also harbored a cleavage site that was not found in atrial appendages from patients in sinus rhythm. This cleavage site preceded the N-terminal domain of decorin that controls muscle growth by altering the binding capacity for myostatin. Myostatin expression was decreased in atrial appendages of patients with persistent atrial fibrillation and hearts of decorin null mice. A synthetic peptide corresponding to this decorin region dose-dependently inhibited the response to myostatin in cardiomyocytes and in perfused mouse hearts. CONCLUSIONS: This proteomics study is the first to analyze the human cardiac ECM. Novel processed forms of decorin protein core, uncovered in human atrial appendages, can regulate the local bioavailability of antihypertrophic and profibrotic growth factors.

Item Type: Article
Additional Information: This is a non-final version of an article published in final form in Barallobre-Barreiro, J; Gupta, SK; Zoccarato, A; Kitazume-Taneike, R; Fava, M; Yin, X; Werner, T; Hirt, MN; Zampetaki, A; Viviano, A; et al. (2016) Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation. Circulation, 134 (11). pp. 817-832.
Keywords: atrial fibrillation, cardiovascular diseases, extracellular matrix, mass spectrometry, proteomics, Animals, Atrial Fibrillation, Decorin, Female, HEK293 Cells, Heart Atria, Heart Ventricles, Humans, Male, Mice, Mice, Mutant Strains, Myocytes, Cardiac, Myostatin, Peptides, Proteomics, atrial fibrillation, cardiovascular diseases, extracellular matrix, mass spectrometry, proteomics, atrial fibrillation heart, cardiovascular disease, extracellular matrix, mass spectrometry, proteomics, Cardiovascular System & Hematology, 1103 Clinical Sciences, 1102 Cardiovascular Medicine And Haematology, 1117 Public Health And Health Services
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Academic Structure > Molecular and Clinical Sciences Research Institute (MCS) > Cardiac (INCCCA)
Journal or Publication Title: Circulation
ISSN: 1524-4539
Language: eng
Dates:
DateEvent
13 September 2016Published
24 August 2016Published Online
27 June 2016Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
FS/13/18/30207British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
FS/13/2/29892British Heart Foundationhttp://dx.doi.org/10.13039/501100000274
J 3679-B13Austrian Science Fundhttp://dx.doi.org/10.13039/501100002428
DFG/SFB 1116Deutsche Forschungsgemeinschafthttp://dx.doi.org/10.13039/501100001659
PubMed ID: 27559042
Web of Science ID: WOS:000384057900012
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109560
Publisher's version: https://doi.org/10.1161/CIRCULATIONAHA.115.016423

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