Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction. Journal Article

Authors: Govindan, S.; McElligott, A.; Muthusamy, S.; Nair, N.; Barefield, D.; Martin, J. L.; Gongora, E.; Greis, K. D.; Luther, P. K.; Winegrad, S.; Henderson, K. K.; Sadayappan, S
Article Title: Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction.
Abstract: Cardiac myosin binding protein-C (cMyBP-C) is a thick filament assembly protein that stabilizes sarcomeric structure and regulates cardiac function; however, the profile of cMyBP-C degradation after myocardial infarction (MI) is unknown. We hypothesized that cMyBP-C is sensitive to proteolysis and is specifically increased in the bloodstream post-MI in rats and humans. Under these circumstances, elevated levels of degraded cMyBP-C could be used as a diagnostic tool to confirm MI. To test this hypothesis, we first established that cMyBP-C dephosphorylation is directly associated with increased degradation of this myofilament protein, leading to its release in vitro. Using neonatal rat ventricular cardiomyocytes in vitro, we were able to correlate the induction of hypoxic stress with increased cMyBP-C dephosphorylation, degradation, and the specific release of N'-fragments. Next, to define the proteolytic pattern of cMyBP-C post-MI, the left anterior descending coronary artery was ligated in adult male rats. Degradation of cMyBP-C was confirmed by a reduction in total cMyBP-C and the presence of degradation products in the infarct tissue. Phosphorylation levels of cMyBP-C were greatly reduced in ischemic areas of the MI heart compared to non-ischemic regions and sham control hearts. Post-MI plasma samples from these rats, as well as humans, were assayed for cMyBP-C and its fragments by sandwich ELISA and immunoprecipitation analyses. Results showed significantly elevated levels of cMyBP-C in the plasma of all post-MI samples. Overall, this study suggests that cMyBP-C is an easily releasable myofilament protein that is dephosphorylated, degraded and released into the circulation post-MI. The presence of elevated levels of cMyBP-C in the blood provides a promising novel biomarker able to accurately rule in MI, thus aiding in the further assessment of ischemic heart disease. Copyright Copyright 2011 Elsevier Ltd. All rights reserved.
Keywords: Aged; Aged, 80 and over; Female; Humans; Middle Aged; Male; Animals; Mice; Disease Models, Animal; Rats; Biological Markers; Cell and Molecular Physiology; Time Factors; Phosphorylation; Rats, Sprague-Dawley; myocardial infarction; Carrier Proteins; Mice, Knockout; Myocardium; Proteolysis; Sarcomeres
Journal Title: Journal of Molecular and Cellular Cardiology
Volume: 52
Issue: 1
ISSN: 1095-8584; 0022-2828
Publisher: Elsevier Inc  
Journal Place: England
Date Published: 2012
Start Page: 154
End Page: 164
Language: English
Notes: ID: 12205; Record Owner: From MEDLINE, a database of the U.S. National Library of Medicine.; Status: MEDLINE; Publishing Model: Journal available in: Print-Electronic Citation processed from: Internet; NLM Journal Code: j72, 0262322; Other ID: Source: NLM. NIHMS327779 [Available on 01/01/13] Source: NLM. PMC3246118 [Available on 01/01/13]; CAS Registry/EC Number/Name of Substance: 0 (Biological Markers). 0 (Carrier Proteins). 0 (myosin-binding protein C).; Grant Number: 5P30HL101297 (United States NHLBI NIH HHS), R01 HL105826-01 (United States NHLBI NIH HHS), R01 HL105826-02 (United States NHLBI NIH HHS), R01HL105826 (United States NHLBI NIH HHS); Electronic Date of Publication: 20110919; Entry Date: 20120424