title: Cardiac myosin-binding protein C: a potential early biomarker of myocardial injury.
abstract: Cardiac troponins are released and cleared slowly after myocardial injury, complicating the diagnosis of early, and recurrent, acute myocardial infarction. Cardiac myosin-binding protein C (cMyC) is a similarly cardiac-restricted protein that may have different release/clearance kinetics. Using novel antibodies raised against the cardiac-specific N-terminus of cMyC, we used confocal microscopy, immunoblotting and immunoassay to document its location and release. In rodents, we demonstrate rapid release of cMyC using in vitro and in vivo models of acute myocardial infarction. In patients, with ST elevation myocardial infarction (STEMI, n = 20), undergoing therapeutic ablation of septal hypertrophy (TASH, n = 20) or having coronary artery bypass surgery (CABG, n = 20), serum was collected prospectively and frequently. cMyC appears in the serum as full-length and fragmented protein. Compared to cTnT measured using a contemporary high-sensitivity commercial assay, cMyC peaks earlier (STEMI, 9.3 ± 3.1 vs 11.8 ± 3.4 h, P < 0.007; TASH, 9.7 ± 1.4 vs 21.6 ± 1.4 h, P < 0.0001), accumulates more rapidly (during first 4 h after TASH, 25.8 ± 1.9 vs 4.0 ± 0.4 ng/L/min, P < 0.0001) and disappears more rapidly (post-CABG, decay half-time 5.5 ± 0.8 vs 22 ± 5 h, P < 0.0001). Our results demonstrate that following defined myocardial injury, the rise and fall in the serum of cMyC is more rapid than that of cTnT. We speculate that these characteristics could enable earlier diagnosis of myocardial infarction and reinfarction in suspected non-STEMI, a population not included in this early translational study.
authors.affiliation: King's College London BHF Centre, The Rayne Institute, St Thomas' Hospital, 4th Floor Lambeth Wing, Westminster Bridge Road, London, SE1 7EH, UK.
authors.forename: James O
authors.initials: JO
authors.lastname: Baker
authors.forename: Raymond
authors.initials: R
authors.lastname: Tyther
authors.forename: Christoph
authors.initials: C
authors.lastname: Liebetrau
authors.forename: James
authors.initials: J
authors.lastname: Clark
authors.forename: Robert
authors.initials: R
authors.lastname: Howarth
authors.forename: Tiffany
authors.initials: T
authors.lastname: Patterson
authors.forename: Helge
authors.initials: H
authors.lastname: Möllmann
authors.forename: Holger
authors.initials: H
authors.lastname: Nef
authors.forename: Pierre
authors.initials: P
authors.lastname: Sicard
authors.forename: Balrik
authors.initials: B
authors.lastname: Kailey
authors.forename: Renuka
authors.initials: R
authors.lastname: Devaraj
authors.forename: Simon R
authors.initials: SR
authors.lastname: Redwood
authors.forename: Gudrun
authors.initials: G
authors.lastname: Kunst
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Weber
authors.forename: Michael S
authors.initials: MS
authors.lastname: Marber
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood*; D002352:Carrier Proteins / Q000097:blood*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D015151:Immunoblotting; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D020349:Surface Plasmon Resonance; D000099163:Myosin Binding Protein C
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D000099163:Myosin Binding Protein C
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