Contractile dysfunction in hypertrophic cardiomyopathy: elucidating primary defects of mutant contractile proteins by gene transfer.

Hypertrophic cardiomyopathy (HCM) is an inherited disorder of cardiac muscle that has been linked to mutations in the contractile proteins that make up the cardiac muscle sarcomere. Recent advances in cardiovascular molecular biology, including gene targeting and transgenesis in mice, and gene transfer technology to adult cardiac myocytes in primary culture, have provided new insights into how these mutations alter the structure-function of the cardiac muscle pump and the molecular mechanisms of HCM pathogenesis. In this review, we highlight the contributions of the application of gene transfer technology to adult cardiac myocytes in vitro that aim at sorting the primary effects of HCM mutant contractile proteins on the structure and function of cardiac muscle cells from the compensatory and secondary phenomenon that occur during HCM pathogenesis in vivo. The elucidation of the primary molecular mechanisms underlying the development of HCM forms a foundation by which to identify the key targets for disease treatment or prevention.