Understanding the molecular basis of HCM-causing mutations in cardiac myosin and cardiac myosin binding protein-C

Abstract

Hypertrophic cardiomyopathy (HCM), a heritable cardiovascular disease marked by hypercontractility and abnormal thickening of heart muscle, affects up to 1 in 200 individuals. Mutations in sarcomere proteins result in HCM, but the mechanism by which these mutant proteins lead to hypercontractility and heart failure remains poorly understood, limiting clinical interventions for the same. We are currently focusing on two sarcomere proteins that together comprise ∼70% of all known HCM mutations: β-cardiac myosin and cardiac myosin binding protein-C, cMyBPC (a regulatory protein in the thick filament).