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

  • Aiko Ogawa
    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.
  • Kazufumi Nakamura
    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.
  • Hiromi Matsubara
    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.
  • Hideki Fujio
    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.
  • Tetsuya Ikeda
    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.
  • Kaoru Kobayashi
    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.
  • Ikuko Miyazaki
    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.
  • Masato Asanuma
    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.
  • Katsumasa Miyaji
    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.
  • Daiji Miura
    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.
  • Kengo Fukushima Kusano
    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.
  • Hiroshi Date
    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.
  • Tohru Ohe
    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.

抄録

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> 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. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> 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 <jats:sup>3</jats:sup> H-thymidine incorporation. PSL (2×10 <jats:sup>−4</jats:sup> and 2×10 <jats:sup>−3</jats:sup> mol/L) significantly inhibited PDGF-stimulated proliferation ( <jats:italic>P</jats:italic> <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 G <jats:sub>0</jats:sub> /G <jats:sub>1</jats:sub> to the S phase. This inhibition was associated with increased p27 expression level. PSL (2×10 <jats:sup>−4</jats:sup> mol/L) also inhibited PDGF-induced SMC migration. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> 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. </jats:p>

収録刊行物

  • Circulation

    Circulation 112 (12), 1806-1812, 2005-09-20

    Ovid Technologies (Wolters Kluwer Health)

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