776-3 Regulation of Basic Fibroblast Growth Factor Gene Expression in Rat Cardiac Microvascular Endothelial Cells and Adult Ventricular Myocytes

Basic fibroblast growth factor (bFGF) has been shown to stimulate protein synthesis in adult rat ventricular myocytes (ARVM) and DNA synthesis in microvascular endothelial cells (CM EC). To determine whether Angiotensin 11 (All) and Endothelin I (ET-1), known as peptides affecting myocyte growth, regulate bFGF gene expression in the myocardium we examined the effects of these two peptide autacoids on bFGF mRNA abundance in both cardiac cell types. Baseline levels for bFGF mRNA in freshly isolated ARVM were 4 to 5 fold lower than in CMEC in RNase protection assays. All (10-6 – 10-8M) and ET-1 (10-8 – 10-10M) increased bFGF mRNA abundance in CMEC and in ARVM in a dose dependent manner that was maximal 4–8 hours after treatment. This effect of All was abolished after coincubation with the angiotensin II receptor antagonist (AT-1) losartan (10-6 M), and the ET-1 response was inhibited by the peptide endothelin type A (ETA) antagonist BO-123 (10-6M). To determine whether bFGF itself autoregulates bFGF mRNA abundance, ARVM and CMEC were treated with rh bFGF (20ng/ml). A ninefold increase in bFGF mRNA was detected, thus indicating positive autoregulation. A marked induction of atrial natriuretic peptide mRNA, known as a molecular marker of phenotype dedifferentiation in hypertrophy, was observed after 24 and 48hrs incubation with rh bFGF in ARVM. Finally, the inflammatory cytokine interleukin 1β (rh IL-1β) upregulates bFGF gene expression in ARVM, a response that could be amplified by interferon γ (rm IFN-γ).Thus, bFGF gene expression in ARVM and CMEC from rat heart is regulated by All and ET-1 through the AT-1 receptor and (ETA) receptor subtypes. The upregulation of bFGF gene transcription in response to various stimuli known to affect myocyte and endothelial growth suggest a role for bFGF as a signalling peptide in the hypertrophic response of adult ventricular myocytes and cardiac microvascular endothelial cells