Myocardial Infarction

Almost 1.6 million people suffered myocardial infarction (MI) in 2011 in both the U.S. and Canada. Despite the advent of modern treatmentoptions, mortality and morbidity post-MI remain at high levels. Patients with suspected MI are grouped into ST-segment elevated or non-ST segment elevated MI based on an ECG assessment. However, electrocardiography analysis suffers from poor sensitivity. Patients who show no signs of apparent non-ST segment elevated MI are diagnosed based on increased blood levels of cardiac troponin I. Such markers of myocardial necrosis are only detectable in the blood 4- 12 hours after the onset of ischemia. Thus, there is an urgent need for an alternative biomarker able to identify MI at an early stage for prompt therapeutic intervention. We are engaged in studies to establish cardiac myosin binding protein-C (cMyBP-C) as an early biomarker of MI. Also, previous studies have shown that phosphorylation of cMyBP-C confers resistance to proteolysis, which provides protection against ischemia-reperfusion injury. However, post-translational modifications of cMyBP-C post-MI and ischemic-reperfusion injury are poorly understood. Consequently, additional studies in the lab have been exploring various post-translational modifications of cMyBP-C in myocardial injury. Determining cMyBP-C degradation and post-translational modifications is a critical step in preventing sarcomere alterations and preserving sarcomere structure and function post-MI as a part of a treatment regime.

References:

• Witayavanitkul N, Ait Mou Y, Kuster DW, Khairallah RJ, Sarkey J, Govindan S, Chen X, Ge Y, Rajan S,Wieczorek DF, Irving T, Westfall MV, de Tombe PP, Sadayappan S Myocardial infarction-induced N-terminal fragment of cMyBP-C impairs myofilament function in Human myocardium. J Biol Chem. 2014 Mar 28;289(13):8818-27
• Kuster D, Cardenas-Ospina A, Miller L, Liebetrau C, Troidl C, Nef HM, Möllmann H, Hamm CW, Pieper KS, Mahaffey KW, Kleiman NS, Stuyvers BD, Marian AJ, Sadayappan S. Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury. Am J Physiol Heart Circ Physiol. 2014 306(4):H547-56.
• Kuster D.W.D, Barefield D, Govindan S and Sadayappan S. A sensitive and specific quantitation method for determination of serum cardiac myosin binding protein-C by electrochemiluminescence immunoassay. J. Vis. Exp. e50786, doi:10.3791/50786 (2013).
• Govindan S, Kuster D.W.D, Lin B, Kahn D.J, Jeske W.P, Walenga J.M, Leya F, Hoppensteadt D, Fareed J and Sadayappan S. Increase in cardiac myosin binding protein-C plasma levels is a sensitive and cardiac-specific biomarker of myocardial infarction. Am J Cardiovasc Dis 2013;3(2):60- 70
• Govindan S, Sarkey J, Xiang J, Sundaresan NR, Gupta MP, de Tombe PP and Sadayappan S. Pathogenic properties of the N-terminal region of cardiac myosin binding protein-C in vitro. J Muscle Res Cell Motil. 2012 May;33(1):17-30.
• Sadayappan S. Cardiac myosin binding protein-C: a potential early-stage, cardiac-specific biomarker of ischemic-reperfusion injury. Biomarkers Med. 2012 6(1), 69–72.
• Govindan S, McElligott A, Muthusamy S, Nair N, Barefield D, Greis KD, Martin JL, Gongora E, Luther PK, Winegrad S, Henderson KK and Sadayappan S.Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction. J Mol Cell Cardiol. 2012; 52(1):154-64.