PEPTIDE GROWTH-FACTORS CAN PROVOKE FETAL CONTRACTILE PROTEIN GENE-EXPRESSION IN RAT CARDIAC MYOCYTES

Cardiac-specific gene expression is intricately regulated in response to developmental, hormonal, and hemodynamic stimuli. To test whether cardiac muscle might be a target for regulation by peptide growth factors, the effect of three growth factors on the actin and myosin gene families was investigated by Northern blot analysis in cultured neonatal rat cardiac myocytes. Transforming growth factor-β1 (TGFβ1, 1 ng/ml) and basic fibroblast growth factor (FGF, 25 ng/ml) elicited changes corresponding to those induced by hemodynamic load. The "fetal" β-myosin heavy chain (MHC) was up-regulated about four-fold, whereas the "adult" aMHC was inhibited > 50-60%; expression of α-skeletal actin increased approximately two-fold, with little or no change in α-cardiac actin. Thus, peptide growth factors alter the program of differentiated gene expression in cardiac myocytes, and are sufficient to provoke fetal contractile protein gene expression, characteristic of pressure-overload hypertrophy. Acidic FGF (25 ng/ml) produced seven-to eightfold reciprocal changes in MHC expression but, unlike either TGF-β1 or basic FGF, inhibited both striated α-actin genes by 70-90%. Expression of vascular smooth muscle α-actin, the earliest a-actin induced during cardiac myogenesis, was increased by all three growth factors. Thus, three α-actin genes demonstrate distinct responses to acidic vs. basic FGF.