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

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Glycoproteomics Reveals Decorin Peptides with Anti-Myostatin Activity in Human Atrial Fibrillation. / Barallobre-Barreiro, Javier; Gupta, Shashi K.; Zoccarato, Anna; Kitazume-Taneike, Rika; Fava, Marika; Yin, Xiaoke; Werner, Tessa; Hirt, Marc N.; Zampetaki, Anna; Viviano, Alessandro; Chong, Mei; Bern, Marshall; Kourliouros, Antonios; Domenech, Nieves; Willeit, Peter; Shah, Ajay M.; Jahangiri, Marjan; Schaefer, Liliana; Fischer, Jens W.; Iozzo, Renato V.; Viner, Rosa; Thum, Thomas; Heineke, Joerg; Kichler, Antoine; Otsu, Kinya; Mayr, Manuel.

In: Circulation (Baltimore), Vol. 134, No. 11, 13.09.2016, p. 817-832.

Research output: Contribution to journalArticle

Harvard

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 (Baltimore), vol. 134, no. 11, pp. 817-832. https://doi.org/10.1161/CIRCULATIONAHA.115.016423

APA

Barallobre-Barreiro, J., Gupta, S. K., Zoccarato, A., Kitazume-Taneike, R., Fava, M., Yin, X., ... Mayr, M. (2016). Glycoproteomics Reveals Decorin Peptides with Anti-Myostatin Activity in Human Atrial Fibrillation. Circulation (Baltimore), 134(11), 817-832. https://doi.org/10.1161/CIRCULATIONAHA.115.016423

Vancouver

Barallobre-Barreiro J, Gupta SK, Zoccarato A, Kitazume-Taneike R, Fava M, Yin X et al. Glycoproteomics Reveals Decorin Peptides with Anti-Myostatin Activity in Human Atrial Fibrillation. Circulation (Baltimore). 2016 Sep 13;134(11):817-832. https://doi.org/10.1161/CIRCULATIONAHA.115.016423

Author

Barallobre-Barreiro, Javier ; Gupta, Shashi K. ; Zoccarato, Anna ; Kitazume-Taneike, Rika ; Fava, Marika ; Yin, Xiaoke ; Werner, Tessa ; Hirt, Marc N. ; Zampetaki, Anna ; Viviano, Alessandro ; Chong, Mei ; Bern, Marshall ; Kourliouros, Antonios ; Domenech, Nieves ; Willeit, Peter ; Shah, Ajay M. ; Jahangiri, Marjan ; Schaefer, Liliana ; Fischer, Jens W. ; Iozzo, Renato V. ; Viner, Rosa ; Thum, Thomas ; Heineke, Joerg ; Kichler, Antoine ; Otsu, Kinya ; Mayr, Manuel. / Glycoproteomics Reveals Decorin Peptides with Anti-Myostatin Activity in Human Atrial Fibrillation. In: Circulation (Baltimore). 2016 ; Vol. 134, No. 11. pp. 817-832.

Bibtex Download

@article{4c3215d0cfbe4fcab6ca0e24caa999d0,
title = "Glycoproteomics Reveals Decorin Peptides with Anti-Myostatin Activity in Human Atrial Fibrillation",
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.",
keywords = "atrial fibrillation, cardiovascular diseases, extracellular matrix, mass spectrometry, proteomics",
author = "Javier Barallobre-Barreiro and Gupta, {Shashi K.} and Anna Zoccarato and Rika Kitazume-Taneike and Marika Fava and Xiaoke Yin and Tessa Werner and Hirt, {Marc N.} and Anna Zampetaki and Alessandro Viviano and Mei Chong and Marshall Bern and Antonios Kourliouros and Nieves Domenech and Peter Willeit and Shah, {Ajay M.} and Marjan Jahangiri and Liliana Schaefer and Fischer, {Jens W.} and Iozzo, {Renato V.} and Rosa Viner and Thomas Thum and Joerg Heineke and Antoine Kichler and Kinya Otsu and Manuel Mayr",
year = "2016",
month = "9",
day = "13",
doi = "10.1161/CIRCULATIONAHA.115.016423",
language = "English",
volume = "134",
pages = "817--832",
journal = "Circulation (Baltimore)",
issn = "0009-7322",
publisher = "American Heart Association, Inc.",
number = "11",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Glycoproteomics Reveals Decorin Peptides with Anti-Myostatin Activity in Human Atrial Fibrillation

AU - Barallobre-Barreiro, Javier

AU - Gupta, Shashi K.

AU - Zoccarato, Anna

AU - Kitazume-Taneike, Rika

AU - Fava, Marika

AU - Yin, Xiaoke

AU - Werner, Tessa

AU - Hirt, Marc N.

AU - Zampetaki, Anna

AU - Viviano, Alessandro

AU - Chong, Mei

AU - Bern, Marshall

AU - Kourliouros, Antonios

AU - Domenech, Nieves

AU - Willeit, Peter

AU - Shah, Ajay M.

AU - Jahangiri, Marjan

AU - Schaefer, Liliana

AU - Fischer, Jens W.

AU - Iozzo, Renato V.

AU - Viner, Rosa

AU - Thum, Thomas

AU - Heineke, Joerg

AU - Kichler, Antoine

AU - Otsu, Kinya

AU - Mayr, Manuel

PY - 2016/9/13

Y1 - 2016/9/13

N2 - 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.

AB - 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.

KW - atrial fibrillation

KW - cardiovascular diseases

KW - extracellular matrix

KW - mass spectrometry

KW - proteomics

UR - http://www.scopus.com/inward/record.url?scp=84984600697&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.115.016423

DO - 10.1161/CIRCULATIONAHA.115.016423

M3 - Article

C2 - 27559042

AN - SCOPUS:84984600697

VL - 134

SP - 817

EP - 832

JO - Circulation (Baltimore)

JF - Circulation (Baltimore)

SN - 0009-7322

IS - 11

ER -

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