Molecular biology of cardiac growth and hypertrophy

Pressure-overload cardiac hypertrophy involves not only cellular growth but also reexpression of an extensive "fetal" program of cardiac-specific genes, providing an intriguing system in which to explore molecular signals which transduce altered load. Fibroblast and transforming growth factors are representative of trophic polypeptides produced by myocardium, which are regulated during cardiac morphogenesis and induced by myocardial ischemia, infarction, and load. Growth factors provoke a pattern of gene expression in cultured cardiac myocytes resembling pressure overload in vivo, implying a possible autocrine or paracrine model of cardiac hypertrophy. Growth-factor inducible cellular oncogenes are also expressed in myocardium, upregulated by hemodynamic load, and encode proteins which modulate the cardiac phenotype, in keeping with a possible functional role in growth factor and load-induced intracellular signalling. Demonstration of physiologic implications of growth factor and cellular oncogene expression in the heart awaits application of new technologies in molecular genetics and could herald novel therapeutic interventions for myocardial disease.