The vascular smooth muscle α-actin gene is reactivated during cardiac hypertrophy provoked by load

Abstract

Cardiac hypertrophy triggered by mechanical load possesses features in common with growth factor signal transduction. A hemodynamic load provokes rapid expression of the growth factor-inducible nuclear oncogene, c-fos, and certain peptide growth factors specifically stimulate the "fetal" cardiac genes associated with hypertrophy, even in the absence of load. These include the gene encoding vascular smooth muscle α-actin, the earliest α-actin expressed during cardiac myogenesis; however, it is not known whether reactivation of the smooth muscle α-actin gene occurs in ventricular hypertrophy. We therefore investigated myocardial expression of the smooth muscle α-actin gene after hemodynamic overload. Smooth muscle α-actin mRNA was discernible 24 h after coarctation and was persistently expressed for up to 30 d. In hypertrophied hearts, the prevalence of smooth muscle α-actin gene induction was 0.909, versus 0.545 for skeletal muscle α-actin (P < 0.05). Ventricular mass after 2 d or more of aortic constriction was more highly correlated with smooth muscle α-actin gene activation (r = 0.852; P = 0.0001) than with skeletal muscle α-actin (r = 0.532; P = 0.009); P < 0.0005 for the difference in the correlation coefficients. Thus, smooth muscle α-actin is a molecular marker of the presence and extent of pressure-overload hypertrophy, whose correlation with cardiac growth at least equals that of skeletal α-actin. Induction of smooth muscle a-actin was delayed and sustained after aortic constriction, whereas the nuclear oncogenes c-jun and junB were expressed rapidly and transiently, providing potential dimerization partners for transcriptional control by c-fos.