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(Circulation. 2005;112:1806-1812.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Prednisolone Inhibits Proliferation of Cultured Pulmonary Artery Smooth Muscle Cells of Patients With Idiopathic Pulmonary Arterial Hypertension

Aiko Ogawa, MD; Kazufumi Nakamura, MD; Hiromi Matsubara, MD; Hideki Fujio, MD; Tetsuya Ikeda, MD; Kaoru Kobayashi; Ikuko Miyazaki, BS; Masato Asanuma, MD; Katsumasa Miyaji, MD; Daiji Miura, MSc; Kengo Fukushima Kusano, MD; Hiroshi Date, MD; Tohru Ohe, MD

From the Departments of Cardiovascular Medicine (A.O., K.N., H.F., T.I., K.K., K.M., D.M., K.F.K., T.O.), Brain Science (I.M., M.A.), and Thoracic and Cancer Surgery (H.D.), Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Division of Cardiology (H.M.), National Hospital Organization Okayama Medical Center, Okayama, Japan.

Correspondence to Aiko Ogawa, MD, Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan. E-mail aiko-oky{at}umin.ac.jp

Received January 14, 2005; revision received June 19, 2005; accepted July 1, 2005.

Background— Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. There is no therapy that specifically inhibits SMC proliferation. Recent studies reported that prednisolone (PSL) inhibits the postangioplasty proliferation of SMCs in atherosclerotic arteries. In this study, we tested the hypothesis that PSL has antiproliferative effects on pulmonary artery SMCs of patients with IPAH.

Methods and Results— Pulmonary artery SMCs were harvested from the pulmonary arteries of 6 patients with IPAH who underwent lung transplantation. Control SMCs were obtained from 5 patients with bronchogenic carcinoma who underwent lung lobectomy. After incubation in the presence of platelet-derived growth factor (PDGF), PSL was added at different concentrations and cell proliferation was assessed by ³H-thymidine incorporation. PSL (2x10^–4 and 2x10^–3 mol/L) significantly inhibited PDGF-stimulated proliferation (P<0.05) of SMCs from patients with IPAH but did not affect cell viability of SMCs, as confirmed by trypan blue staining. In cell cycle analysis using a microscope-based multiparameter laser scanning cytometer, PSL inhibited the progression of SMCs from G₀/G₁ to the S phase. This inhibition was associated with increased p27 expression level. PSL (2x10^–4 mol/L) also inhibited PDGF-induced SMC migration.

Conclusions— Our results indicate that PSL has an antiproliferative effect on cultured SMCs of pulmonary arteries from patients with IPAH and suggest that PSL may be potentially useful therapeutically in patients with IPAH.

Key Words: prednisolone • myocytes • hypertension, pulmonary • muscle, smooth

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