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

Hypertrophic cardiomyopathy (HCM) is an inherited disorder of cardiac muscl e that has been linked to mutations in the contractile proteins that make u p the cardiac muscle sarcomere. Recent advances in cardiovascular molecular biology, including gene targeting and transgenesis in mice, and gene trans fer technology to adult cardiac myocytes in primary culture, have provided new insights into how these mutations alter the structure-function of the c ardiac muscle pump and the molecular mechanisms of HCM pathogenesis. In thi s review, we highlight the contributions of the application of gene transfe r technology to adult cardiac myocytes in vitro that aim at sorting the pri mary effects of HCM mutant contractile proteins on the structure and functi on of cardiac muscle cells from the compensatory and secondary phenomenon t hat occur during HCM pathogenesis in vivo. The elucidation of the primary m olecular mechanisms underlying the development of HCM forms a foundation by which to identify the key targets for disease treatment or prevention. (Tr ends Cardiovasc Med 2000;10:177-182). (C) 2001, Elsevier Science Inc. All r ights reserved.