S100-BETA INHIBITS ALPHA(1)-ADRENERGIC INDUCTION OF THE HYPERTROPHIC PHENOTYPE IN CARDIAC MYOCYTES

In an experimental rat model of myocardial infarction, surviving cardi ac myocytes undergo hypertrophy in response to trophic effecters. This response involves gene reprogramming manifested by the re-expression of fetal genes, such as the previously reported isoform switch from ad ult alpha- to embryonic beta-myosin heavy chain. We now report the tra nsient re-expression of a second fetal gene, skeletal alpha-actin in r at myocardium at 7 days post-infarction, and its subsequent down-regul ation coincident with the delayed induction of S100 beta, a protein no rmally expressed in brain. In cultured neonatal rat cardiac myocytes, co-transfection with an S100 beta-expression vector inhibits a pathway associated with hypertrophy, namely, alpha(1)-adrenergic induction of beta-myosin heavy chain and skeletal alpha-actin promoters mediated b y beta-protein kinase C. The induction of beta-myosin heavy chain by h ypoxia was similarly blocked by forced expression of S100 beta. Our re sults suggest that S100 beta may be an intrinsic negative regulator of the hypertrophic response of surviving cardiac myocytes post-infarcti on. Such negative regulators may be important in limiting the adverse consequences of unchecked hypertrophy leading to ventricular remodelin g and dysfunction.