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Cardiac myosin-binding protein C: a potential early biomarker of myocardial injury.

Baker JO, Tyther R, Liebetrau C, Clark J, Howarth R, Patterson T, Möllmann H, Nef H, Sicard P, Kailey B, Devaraj R, Redwood SR, Kunst G, Weber E, Marber MS - Basic Res. Cardiol. (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: King's College London BHF Centre, The Rayne Institute, St Thomas' Hospital, 4th Floor Lambeth Wing, Westminster Bridge Road, London, SE1 7EH, UK.

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.

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The relationship between cMyC and cTnT. The maximum serum concentration achieved for cMyC and cTnT in the series of blood draws for patients undergoing TASH (open symbols) or CABG (closed symbols) was compared by linear regression. R2 = 0.30, P < 0.0001, [cTnT] = 0.11x[cMyC] + 845
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Fig6: The relationship between cMyC and cTnT. The maximum serum concentration achieved for cMyC and cTnT in the series of blood draws for patients undergoing TASH (open symbols) or CABG (closed symbols) was compared by linear regression. R2 = 0.30, P < 0.0001, [cTnT] = 0.11x[cMyC] + 845

Mentions: To gain some idea of the comparative concentrations of cMyC and cTnT, in Fig. 6, we compared the peak concentration achieved for each biomarker in the CABG (closed symbols) and TASH (open symbols) cohorts. There is a reasonable correlation between peak cTnT and peak cMyC (see Fig. 6, R2 = 0.3, P < 0.0001) which compares favorably with the best correlation between four high sensitivity cTn assays applied to a healthy population (R2 = 0.08) [2]. This relationship is closest for the CABG cohort, since it is likely the peak cTnT concentration was not recorded in the TASH cohort (occurred after 24 h). On average, the peak cMyC concentration is fivefold greater than the peak cTn concentration, despite cMyC calibration with a fragment rather than with the full-length protein.Fig. 6


Cardiac myosin-binding protein C: a potential early biomarker of myocardial injury.

Baker JO, Tyther R, Liebetrau C, Clark J, Howarth R, Patterson T, Möllmann H, Nef H, Sicard P, Kailey B, Devaraj R, Redwood SR, Kunst G, Weber E, Marber MS - Basic Res. Cardiol. (2015)

The relationship between cMyC and cTnT. The maximum serum concentration achieved for cMyC and cTnT in the series of blood draws for patients undergoing TASH (open symbols) or CABG (closed symbols) was compared by linear regression. R2 = 0.30, P < 0.0001, [cTnT] = 0.11x[cMyC] + 845
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4383815&req=5

Fig6: The relationship between cMyC and cTnT. The maximum serum concentration achieved for cMyC and cTnT in the series of blood draws for patients undergoing TASH (open symbols) or CABG (closed symbols) was compared by linear regression. R2 = 0.30, P < 0.0001, [cTnT] = 0.11x[cMyC] + 845
Mentions: To gain some idea of the comparative concentrations of cMyC and cTnT, in Fig. 6, we compared the peak concentration achieved for each biomarker in the CABG (closed symbols) and TASH (open symbols) cohorts. There is a reasonable correlation between peak cTnT and peak cMyC (see Fig. 6, R2 = 0.3, P < 0.0001) which compares favorably with the best correlation between four high sensitivity cTn assays applied to a healthy population (R2 = 0.08) [2]. This relationship is closest for the CABG cohort, since it is likely the peak cTnT concentration was not recorded in the TASH cohort (occurred after 24 h). On average, the peak cMyC concentration is fivefold greater than the peak cTn concentration, despite cMyC calibration with a fragment rather than with the full-length protein.Fig. 6

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: King's College London BHF Centre, The Rayne Institute, St Thomas' Hospital, 4th Floor Lambeth Wing, Westminster Bridge Road, London, SE1 7EH, UK.

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.

Show MeSH
Related in: MedlinePlus