Disease Pathways and Novel Therapeutic Targets in Hypertrophic Cardiomyopathy

As described in earlier reviews in this series on the molecular basis of hypertrophic cardiomyopathy (HCM), HCM is one of the archetypal monogenic cardiovascular disorders still confirm that HCM is principally a disease of the sarcomere. At the biophysical level, myofilament mutations generally enhance Ca2+ sensitivity, maximal force production, and ATPase activity. These defects ultimately appear to converge on energy deficiency and altered Ca2+ handling as major common paths leading to the anatomic (hypertrophy myofiber disarray, and fibrosis) and functional features (pathological signaling and diastolic dysfunction) HCM mutations and describe how specifically targeting these molecular features has already yielded early promise for novel therapies for HCM. Although substantial efforts are still required to understand the molecular link between HCM mutations and HCM. Although substantial efforts are still required to understand the molecular link between HCM mutations and their clinical consequences. HCM endures as an exemplar of how novel insights derived from molecular characterization of Mendelian disorders can inform the understanding of biological processes and translate into rational therapies. (Circ Res. 2011;109:86-96.)