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 proteoly...

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Bibliographic Details
Published in:Journal of molecular and cellular cardiology 2012-01, Vol.52 (1), p.154-164
Main Authors: Govindan, Suresh, McElligott, Andrew, Muthusamy, Saminathan, Nair, Nandini, Barefield, David, Martin, Jody L, Gongora, Enrique, Greis, Kenneth D, Luther, Pradeep K, Winegrad, Saul, Henderson, Kyle K, Sadayappan, Sakthivel
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Animals
Biomarkers - metabolism
Cardiac biomarker
Cardiac troponin I
Cardiovascular
Carrier Proteins - chemistry
Carrier Proteins - genetics
Carrier Proteins - metabolism
Disease Models, Animal
Female
Humans
Male
Mice
Mice, Knockout
Middle Aged
Myocardial Infarction - diagnosis
Myocardial Infarction - genetics
Myocardial Infarction - metabolism
Myocardium - metabolism
Myocardium - pathology
Myosin binding protein-C
Phosphorylation
Proteolysis
Rats
Rats, Sprague-Dawley
Sandwich ELISA assay
Sarcomeres - metabolism
Time Factors
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Summary: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.
ISSN:0022-2828
1095-8584
DOI:10.1016/j.yjmcc.2011.09.011