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Updated: Mar 15, 2026
Glycoproteomics of the Extracellular Matrix: A Method for Intact Glycopeptide Analysis Using Mass Spectrometry
Published on: April 21, 2017
Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin Activity in Human Atrial Fibrillation
Javier Barallobre-Barreiro1, Shashi K Gupta1, Anna Zoccarato1
1From King's British Heart Foundation Centre, King's College London, United Kingdom (J.B.-B., A. Zoccarato, R.K.-T., M.F., X.Y., A. Zampetaki, M.C., P.W., A.M.S., K.O., M.M.); Institute for Molecular and Translational Therapeutic Strategies, MH-Hannover, Germany (S.K.G., T.T.); St George's Hospital, NHS Trust, London, United Kingdom (M.F., A.V., A.K., M.J.); University Medical Center Hamburg-Eppendorf, Germany (T.W., M.N.H.); Protein Metrics, San Carlos, CA (M.B.); Biobanco A Coruña, INIBIC-Complexo Hospitalario Universitario de A Coruña, Spain (N.D.); Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt, Frankfurt am Main, Germany (L.S.); Institute for Pharmacology and Clinical Pharmacology, Heinrich-Heine-University, Düsseldorf, Germany (J.W.F.); Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA (R.V.I.); Thermo Fisher Scientific, San Jose, CA (R.V.); Experimental Cardiology, Department of Cardiology and Angiology, MH-Hannover, Germany (J.H.); and Laboratoire Vecteurs: Synthèse et Applications Thérapeutiques, UMR 7199 CNRS Université de Strasbourg, Illkirch, France (A.K.).
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.
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