MOLECULAR-BIOLOGY OF CARDIAC GROWTH AND HYPERTROPHY

Pressure-overload cardiac hypertrophy involves not only cellular growt h but also reexpression of an extensive ''fetal'' program of cardiac-s pecific genes, providing an intriguing system in which to explore mole cular signals which transduce altered load. Fibroblast and transformin g growth factors are representative of trophic polypeptides produced b y myocardium, which are regulated during cardiac morphogenesis and ind uced by myocardial ischemia, infarction, and load. Growth factors prov oke a pattern of gene expression in cultured cardiac myocytes resembli ng pressure overload in vivo, implying a possible autocrine or paracri ne model of cardiac hypertrophy. Growth-factor inducible cellular onco genes are also expressed in myocardium, upregulated by hemodynamic loa d, and encode proteins which modulate the cardiac phenotype, in keepin g with a possible functional role in growth factor and load-induced in tracellular signalling. Demonstration of physiologic implications of g rowth factor and cellular oncogene expression in the heart awaits appl ication of new technologies in molecular genetics and could herald nov el therapeutic interventions for myocardial disease.