title: Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury.
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.
authors: Department of Cell and Molecular Physiology, Health Sciences Division, Loyola University Chicago, Maywood, Illinois;
authors: Diederik W D
authors: DW
authors: Kuster
authors: Adriana
authors: A
authors: Cardenas-Ospina
authors: Lawson
authors: L
authors: Miller
authors: Christoph
authors: C
authors: Liebetrau
authors: Christian
authors: C
authors: Troidl
authors: Holger M
authors: HM
authors: Nef
authors: Helge
authors: H
authors: Möllmann
authors: Christian W
authors: CW
authors: Hamm
authors: Karen S
authors: KS
authors: Pieper
authors: Kenneth W
authors: KW
authors: Mahaffey
authors: Neal S
authors: NS
authors: Kleiman
authors: Bruno D
authors: BD
authors: Stuyvers
authors: Ali J
authors: AJ
authors: Marian
authors: Sakthivel
authors: S
authors: Sadayappan
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D004195:Disease Models, Animal; D006801:Humans; D007700:Kinetics; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis*; D013552:Swine; D019210:Troponin I / Q000097:blood; D020107:Troponin T / Q000097:blood; D000099163:Myosin Binding Protein C
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D019210:Troponin I; D020107:Troponin T; D000099163:Myosin Binding Protein C
keywords: MYBPC3; acute coronary syndrome; biomarker; cMyBP-C; cardiac troponin I; myocardial infarction