Carvedilol inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension

Hideki Fujio, Kazufumi Nakamura, Hiromi Matsubara, Kengo Fukushima Kusano, Katsumasa Miyaji, Satoshi Nagase, Tetsuya Ikeda, Aiko Ogawa, Keiko Ohta-Ogo, Daiji Miura, Aya Miura, Masahiro Miyazaki, Hiroshi Date, Tohru Ohe

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Idiopathic pulmonary arterial hypertension (IPAH) is associated with proliferation of smooth muscle cells (SMCs) in small pulmonary arteries. Inhibition of proliferation of pulmonary artery smooth muscle cells (PASMCs) may be an effective treatment of patients with idiopathic pulmonary arterial hypertension. Recent studies have shown that carvedilol, an α- and β-blocker with antioxidant and calcium channel blocking properties, inhibits the proliferation of cultured normal human pulmonary artery smooth muscle cells. In this study, we tested the hypothesis that carvedilol has antiproliferative effects on pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Pulmonary artery smooth muscle cells from six idiopathic pulmonary arterial hypertension patients who had undergone lung transplantation were cultured. To determine cell proliferation, H-thymidine incorporation was measured. Platelet-derived growth factor-induced proliferation of IPAH-PASMCs was significantly greater than that of normal control pulmonary artery smooth muscle cells. Carvedilol (0.1 μM to 10 μM) inhibited the proliferation of idiopathic pulmonary arterial hypertension-pulmonary artery smooth muscle cells in a concentration-dependent manner. Prazosin (an α-blocker) and N-acetyl L cysteine (an antioxidant agent) (0.1 μM to 10 μM) did not inhibit their proliferation, but the high concentration of propranolol (a β-blocker) and nifedipine (a calcium channel blocker) (10 μM) inhibited the proliferation. The combination of propranolol and nifedipine inhibited the proliferation but only at a high concentration (10 μM) combination. Cell cycle analysis revealed that carvedilol (10 μM) significantly decreased the number of cells in S and G2/M phases. These results indicate that carvedilol inhibits the exaggerated proliferation of pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension partially via its α-blocking and calcium channel blocking effects in vitro.

Original languageEnglish
Pages (from-to)250-255
Number of pages6
JournalJournal of cardiovascular pharmacology
Volume47
Issue number2
DOIs
Publication statusPublished - Feb 2006

Keywords

  • Carvedilol
  • Cell cycle
  • Cell proliferation
  • Idiopathic pulmonary arterial hypertension (IPAH)
  • Lung transplantation
  • Smooth muscle cells

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Fujio, H., Nakamura, K., Matsubara, H., Kusano, K. F., Miyaji, K., Nagase, S., Ikeda, T., Ogawa, A., Ohta-Ogo, K., Miura, D., Miura, A., Miyazaki, M., Date, H., & Ohe, T. (2006). Carvedilol inhibits proliferation of cultured pulmonary artery smooth muscle cells of patients with idiopathic pulmonary arterial hypertension. Journal of cardiovascular pharmacology, 47(2), 250-255. https://doi.org/10.1097/01.fjc.0000201359.58174.c8