ANTISENSE FOSB RNA INHIBITS THROMBIN-INDUCED HYPERTROPHY IN CULTURED PULMONARY ARTERIAL SMOOTH-MUSCLE CELLS

Background-We have previously reported that fosB mRNA is induced by hy pertrophic stimuli (thrombin, angiotensin LI) but not proliferative st imuli (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 pot ential role of FosB in PASMC hypertrophy. Methods and Results-Adenovir uses carrying sense or antisense fosB RNA expression cassettes were us ed to infect cultured PASMCs with the aim of increasing or inhibiting fosB expression, respectively. We examined whether fosB expression mod ification affected the growth of quiescent PASMCs, thrombin-induced hy pertrophy, or platelet-derived growth factor-induced proliferation. PA SMC growth was assessed by daily cell number count, determination of [ H-3]leucine incorporation, and quantification of total cellular protei n. Neither an increase nor a decrease in FosB protein expression cause d a significant change in the growth of quiescent PASMCs over a period of 96 hours, indicating that FosB alone is not sufficient to induce h ypertrophy. Modification of FosB levels did not affect platelet-derive d growth factor-induced PASMC proliferation. An increase in FosB expre ssion did not augment thrombin-induced hypertrophy; however, inhibitio n of FosB expression resulted in a diminution of thrombin-induced hype rtrophy by 58 +/- 6% (P < 0.005). Conclusions-These results suggest th at FosB is necessary but not sufficient fur thrombin-induced hypertrop hy in cultured PASMCs.