S100β inhibits α1-adrenergic induction of the hypertrophic phenotype in cardiac myocytes

Abstract

In an experimental rat model of myocardial infarction, surviving cardiac myocytes undergo hypertrophy in response to trophic effectors. This response involves gene reprogramming manifested by the re-expression of fetal genes, such as the previously reported isoform switch from adult α- to embryonic β-myosin heavy chain. We now report the transient re-expression of a second fetal gene, skeletal α-actin in rat myocardium at 7 days post-infarction, and its subsequent down-regulation coincident with the delayed induction of S100β, a protein normally expressed in brain. In cultured neonatal rat cardiac myocytes, co-transfection with an S100β-expression vector inhibits a pathway associated with hypertrophy, namely, α1-adrenergic induction of β- myosin heavy chain and skeletal α-actin promoters mediated by β-protein kinase C. The induction of β-myosin heavy chain by hypoxia was similarly blocked by forced expression of S100β. Our results suggest that S100β may be an intrinsic negative regulator of the hypertrophic response of surviving cardiac myocytes post-infarction. Such negative regulators may be important in limiting the adverse consequences of unchecked hypertrophy leading to ventricular remodeling and dysfunction.