Antisense fos B RNA Inhibits Thrombin-Induced Hypertrophy in Cultured Pulmonary Arterial Smooth Muscle Cells

Abstract

Background —We have previously reported that fos B mRNA is induced by hypertrophic stimuli (thrombin, angiotensin II) but not proliferative stimuli (platelet-derived growth factor, basic fibroblast growth factor) in pulmonary arterial smooth muscle cells (PASMCs) ( J Biol Chem . 1994;9:6399–6404). Our aim in the present study was to investigate the potential role of FosB in PASMC hypertrophy. Methods and Results —Adenoviruses carrying sense or antisense fos B RNA expression cassettes were used to infect cultured PASMCs with the aim of increasing or inhibiting fos B expression, respectively. We examined whether fos B expression modification affected the growth of quiescent PASMCs, thrombin-induced hypertrophy, or platelet-derived growth factor–induced proliferation. PASMC growth was assessed by daily cell number count, determination of [ 3 H]leucine incorporation, and quantification of total cellular protein. Neither an increase nor a decrease in FosB protein expression caused a significant change in the growth of quiescent PASMCs over a period of 96 hours, indicating that FosB alone is not sufficient to induce hypertrophy. Modification of FosB levels did not affect platelet-derived growth factor–induced PASMC proliferation. An increase in FosB expression did not augment thrombin-induced hypertrophy; however, inhibition of FosB expression resulted in a diminution of thrombin-induced hypertrophy by 58±6% ( P <0.005). Conclusions —These results suggest that FosB is necessary but not sufficient for thrombin-induced hypertrophy in cultured PASMCs.