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(Circulation. 1998;98:596-603.)
© 1998 American Heart Association, Inc.

Basic Science Reports

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

Chuanyi Lu, MD; Frank J. Giordano, MD; Xuping Bao, MD; Kemberlyn C. Morris, BS; ; Abraham Rothman, MD

From the Molecular Cardiology Laboratory, Department of Pediatrics (C.L., X.B., K.C.M., A.R.) and Department of Medicine (F.J.G.), University of California San Diego School of Medicine, La Jolla.

Correspondence to Abraham Rothman, MD, Division of Pediatric Cardiology, PO Box 8445, UCSD Medical Center, 200 W Arbor Dr, San Diego, CA 92103-8445. E-mail abrothman{at}ucsd.edu

Background—We have previously reported that fosB 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 fosB RNA expression cassettes were used to infect cultured PASMCs with the aim of increasing or inhibiting fosB expression, respectively. We examined whether fosB 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 [³H]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.

Key Words: muscle, smooth • hypertrophy • growth substances • RNA

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