Implications of the complex biology and micro-environment of cardiac sarcomeres in the use of high affinity troponin antibodies as serum biomarkers for cardiac disorders.

ABSTRACT

Cardiac troponin I (cTnI), the inhibitory-unit, and cardiac troponin T (cTnT), the tropomyosin-binding unit together with the Ca-binding unit (cTnC) of the hetero-trimeric troponin complex signal activation of the sarcomeres of the adult cardiac myocyte. The unique structure and heart myocyte restricted expression of cTnI and cTnT led to their worldwide use as biomarkers for acute myocardial infarction (AMI) beginning more than 30 years ago. Over these years, high sensitivity antibodies (hs-cTnI and hs-cTnT) have been developed. Together with careful determination of history, physical examination, and EKG, determination of serum levels using hs-cTnI and hs-cTnT permits risk stratification of patients presenting in the Emergency Department (ED) with chest pain. With the ability to determine serum levels of these troponins with high sensitivity came the question of whether such measurements may be of diagnostic and prognostic value in conditions beyond AMI. Moreover, the finding of elevated serum troponins in physiological states such as exercise and pathological states where cardiac myocytes may be affected requires understanding of how troponins may be released into the blood and whether such release may be benign. We consider these questions by relating membrane stability to the complex biology of troponin with emphasis on its sensitivity to the chemo-mechanical and micro-environment of the cardiac myocyte. We also consider the role determinations of serum troponins play in the precise phenotyping in personalized and precision medicine approaches to promote cardiac health.