Patented biomarker for cardiac injury. 

Patented biomarker for cardiac injury. 

Category: Scientific background

The structure demonstrates that MyBP-C bridges thin and thick filaments, with its carboxy-terminal region binding to the myosin tails and directly stabilizing the OFF state of the myosin heads in an unforeseen manner.
Here we solve the structure of the main (cMyBP-C-containing) region of the human cardiac filament using cryo-electron microscopy. The reconstruction reveals the architecture of titin and cMyBP-C and shows how myosin’s motor domains (heads) form three different types of motif (providing functional flexibility), which interact with each other and with titin and cMyBP-C to dictate filament architecture and function.
Cardiac myosin-binding protein C (cMyBP-C, MYBPC3, cMyC; UniProtKB—Q14896) is a 140 kDa sarcomeric protein that is loosely associated with both myosin and actin. It was identified in the coronary effluent from ischaemic myocardium about 10 years ago and after systematic screening of monoclonal antibodies a sensitive sandwich immunoassay was formulated. Using this assay, cMyC has been measured in a variety of patient groups and directly compared to cardiac troponin T (cTnT) and cardiac troponin I (cTnI) measured in the same blood samples using high-sensitivity assays.
cMyC is mentioned in the 2020 ESC Guidelines for the management of acute coronary syndromes in NSTEMI patients as an alternative to troponin.
cMyC is more abundant than Troponin and provides discriminatory power comparable to hs-cTnT/I for the diagnosis of AMI in all-comers, and identifies a greater proportion of patients with AMI in very early presenters. A standout feature is cMyC’s ability to more effectively triage patients. This distinction is likely related to the documented greater abundance and more rapid release profile of cMyC. If used on a POCT platform, cMyC could significantly improve the early triage of patients with suspected AMI.
We examined how many myocytes and how much myocardium these concentrations represent. We also examined if dietary troponin can confound the rule-out algorithm. Based on pragmatic assumptions regarding cTn and cMyC release efficiency, circulating species, and volume of distribution, 99th centile concentrations may be exceeded by necrosis of 40 mg of myocardium. This volume is much too small to detect by noninvasive imaging.
The cMyC assay is very sensitive, cMyC concentration is closely related to hs-cTnT and hs-cTnI and seems perturbed by the same sorts of things (renal dysfunction, age, poor LV function).
cMyC release following cardiac surgical interventions shows a similar time release pattern as Troponins but rises faster to detectable levels.
Discovery of cMyC in the coronary effluent after myocardial infarction.