Rise in Blood Levels of Heart Muscle Protein an Early Diagnostic Marker for Cardiac Injury

The heart muscle protein cMyBP-C (cardiac myosin binding protein-C) is rapidly released into the bloodstream after cardiac damage and may be a sensitive biomarker for diagnosing the onset of myocardial infarction (MI).

Myosin-binding protein C is a myosin-associated protein found in the cross-bridge-bearing zone (C region) of A bands in striated muscle. It is found at regularly spaced intervals and is hypothesized to act like a "barrel hoop" and hold the thick filament together. cMyBP-C, the cardiac isoforms of the protein, is expressed exclusively in heart muscle.

Detection of elevated plasma cardiac troponin (cTn) levels is the "gold standard" for early discovery of MI. However, troponin levels peak only four to six hours after heart attack and lack the sensitivity required to detect the onset of MI at its earliest stages.

Investigators at the Loyola University School of Medicine (Chicago, IL, USA) sought to evaluate the usefulness of cMYBP-C as an ultra-early biomarker of MI. To this end, they studied the release kinetics of cMyBP-C in a porcine model of MI and in two human cohorts.

They measured cMyBP-C levels in serum and plasma samples from MI pigs and patients serially from 30 minutes to 14 days after coronary damage using a custom immunoassay based on electrochemiluminescence. The anti-cMyBP-C antibodies used in this study were specific to cMyBP-C and were generated against the C0 domain of cMyBP-C, which is exclusively present in the cardiac isoform and does not cross react with skeletal MyBP-C isoforms. The assay was comparable to a previously described ELISA and used the same capture and detection antibodies. The chemiluminescence immunoassay had improved sensitivity, compared to ELISA.

Results revealed that in the pig model system cMyBP-C plasma levels were increased from baseline (around 76 nanograms per liter) to about 767 nanograms per liter three hours after onset of cardiac damage and then peaked at about 2,418 nanograms per liter after six hours. Plasma troponin and myosin light chain levels were all increased after six hours. In a cohort of 12 patients with hypertrophic obstructive cardiomyopathy, cMyBP-C was significantly increased from baseline about 49 nanograms per liter in a time-dependent manner, peaking at about 560 nanograms per liter after four hours. In a second cohort of 176 patients with non-ST segment elevation, cMyBP-C serum levels were significantly higher (about 7,615 nanograms per liter) than those in a control cohort of 153 normal individuals (about 416 nanograms per liter).

“This is a potential ultra-early biomarker that could confirm whether a patient has had a heart attack, leading to faster and more effective treatment,” said senior author Dr. Sakthivel Sadayappan, assistant professor of cell and molecular physiology at Loyola University School of Medicine. “These findings suggest that cMyBP-C has potential as an ultra-early biomarker for the diagnosis of [heart attack], but this still needs to be validated using a large cohort study. A cMyBP-C blood test might lead to an earlier diagnosis in patients who present at the emergency department shortly after coronary artery blockage. However, a systemic prospective investigation is required to establish such data for clinical use.”

The study was published in the February 15, 2014, issue of the American Journal of Physiology – Heart and Circulatory Physiology.

The investigators’ discussion of their work and the importance of their result may be found online (Please see related links below).

Related Links:
Loyola University School of Medicine
The investigators discuss their work and the importance of the results (Audio link Courtesy of the American Physiological Society)