Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury

Diederik W.D. Kuster, Adriana Cardenas-Ospina, Lawson Miller, Christoph Liebetrau, Christian Troidl, Holger M. Nef, Helge Möllmann, Christian W. Hamm, Karen S. Pieper, Kenneth W. Mahaffey, Neal S. Kleiman, Bruno D. Stuyvers, Ali J. Marian, Sakthivel Sadayappan

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Diagnosis of myocardial infarction (MI) is based on ST-segment elevation on electrocardiographic evaluation and/or elevated plasma cardiac troponin (cTn) levels. However, troponins lack the sensitivity required to detect the onset of MI at its earliest stages. Therefore, to confirm its viability as an ultra-early biomarker of MI, this study investigates the release kinetics of cardiac myosin binding protein-C (cMyBP-C) in a porcine model of MI and in two human cohorts. Release kinetics of cMyBP-C were determined in a porcine model of MI (n = 6, pigs, either sex) by measuring plasma cMyBP-C level serially from 30 min to 14 days after coronary occlusion, with use of a custom-made immunoassay. cMyBP-C plasma levels were increased from baseline (76 ± 68 ng/l) at 3 h (767 ± 211 ng/l) and peaked at 6 h (2,418 ± 780 ng/l) after coronary ligation. Plasma cTnI, cTnT, and myosin light chain-3 levels were all increased 6 h after ligation. In a cohort of patients (n = 12) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy, cMyBP-C was significantly increased from baseline (49 ± 23 ng/l) in a time-dependent manner, peaking at 4 h (560 ± 273 ng/l). In a cohort of patients with non-ST segment elevation MI (n = 176) from the SYNERGY trial, cMyBP-C serum levels were significantly higher (7,615 ± 4,514 ng/l) than those in a control cohort (416 ± 104 ng/l; n = 153). cMyBP-C is released in the blood rapidly after cardiac damage and therefore has the potential to positively mark the onset of MI.

Original languageEnglish (US)
Pages (from-to)H547-H556
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume306
Issue number4
DOIs
StatePublished - Feb 15 2014

Keywords

  • Acute coronary syndrome
  • Biomarker
  • Cardiac troponin I
  • cMyBP-C
  • MYBPC3
  • Myocardial infarction

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

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