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Surviving the infarct: A profile of cardiac myosin binding protein-C pathogenicity, diagnostic utility, and proteomics in the ischemic myocardium.
MedLine Citation:
PMID:  24888514     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiac myosin binding protein-C (cMyBP-C) is a regulatory protein of the contractile apparatus within the cardiac sarcomere. Ischemic injury to the heart during myocardial infarction (MI) results in the cleavage of cMyBP-C in a phosphorylation-dependent manner and release of an N-terminal fragment (C0C1f) into the circulation. C0C1f has been shown to be pathogenic within cardiac tissue, leading to the development of heart failure (HF). Based on its high levels and early release into the circulation post-MI, C0C1f may serve as a novel biomarker for diagnosing MI more effectively than current clinically used biomarkers. Over time, circulating C0C1f could trigger an autoimmune response leading to myocarditis and progressive cardiac dysfunction. Given the importance of cMyBP-C phosphorylation state in the context of proteolytic cleavage and release into the circulation post-MI, understanding the post-translational modifications (PTMs) of cMyBP-C would help in further elucidating the role of this protein in health and disease. Accordingly, recent studies have implemented the latest proteomics approaches to define the PTMs of cMyBP-C. The use of such proteomics assays may provide accurate quantitation of the levels of cMyBP-C in the circulation following MI, which could, in turn, demonstrate the efficacy of using plasma cMyBP-C as a cardiac-specific early biomarker of MI. In this review, we define the pathogenic and potential immunogenic effects of C0C1f on cardiac function in the post-MI heart. We also discuss the most advanced proteomics approaches now used to determine cMyBP-C PTMs with the aim of validating C0C1f as an early biomarker of MI. This article is protected by copyright. All rights reserved.
Authors:
Thomas L Lynch; Sakthivel Sadayappan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-5-28
Journal Detail:
Title:  Proteomics. Clinical applications     Volume:  -     ISSN:  1862-8354     ISO Abbreviation:  Proteomics Clin Appl     Publication Date:  2014 May 
Date Detail:
Created Date:  2014-6-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101298608     Medline TA:  Proteomics Clin Appl     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
This article is protected by copyright. All rights reserved.
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