Nifedipine Interferes with Migration of Vascular Smooth Muscle Cells via Inhibition of Pyk2-Src Axis

  • Soe Nwe Nwe
    Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  • Ishida Takafumi
    Departments of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  • Ishida Mari
    Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  • Sawano Mariko
    Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  • Abe Keiko
    Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  • Miho Narimasa
    Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  • Chayama Kazuaki
    Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  • Kihara Yasuki
    Departments of Cardiovascular Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
  • Yoshizumi Masao
    Department of Cardiovascular Physiology and Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan

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Aim: Calcium channel blockers (CCBs) inhibit the migration of vascular smooth muscle cells (VSMC) by mechanisms that remain poorly understood. The purpose of the present study was to characterize the signaling mechanisms by which CCBs inhibit VSMC migration.<BR>Methods and Results: Nifedipine potently inhibited platelet-derived growth factor (PDGF)-induced chemotaxis, collagen I-induced haptotaxis, and wound-induced migration of human aortic VSMC. In addition, nifedipine inhibited PDGF-induced membrane ruffling and lamellipodium formation. PDGF-induced VSMC migration was significantly inhibited by PP2, a selective inhibitor of the Src kinase family, and was also significantly inhibited by the expression of kinase-inactive Src, suggesting that Src is required for VSMC migration. Nifedipine also inhibited PDGF-induced Src activation (by 60±4% with 30 µM) and tyrosinephosphorylation of Cas, paxillin, and cortactin, which are actin-associated substrates of Src. RNA interference-induced knockdown of the Ca2+-dependent tyrosine kinase, Pyk2, resulted in inhibition of PDGF-induced Src activation and migration. Finally, nifedipine inhibited PDGF-induced Pyk2 activation in a dose-dependent manner.<BR>Conclusion: These data suggest that nifedipine interferes with VSMC migration via inhibition of the Pyk2-Src axis and inhibition of actin remodeling processes, including membrane ruffling and lamellipodium formation.

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詳細情報

  • CRID
    1390282679408812800
  • NII論文ID
    10025765621
    130004444280
  • NII書誌ID
    AA11018976
  • DOI
    10.5551/jat.e422
  • COI
    1:CAS:528:DC%2BD1MXpt1ehsbo%3D
  • ISSN
    18803873
    13403478
    http://id.crossref.org/issn/13403478
  • Web Site
    https://search.jamas.or.jp/link/ui/2010041095
  • 本文言語コード
    en
  • データソース種別
    • JaLC
    • Crossref
    • CiNii Articles
  • 抄録ライセンスフラグ
    使用不可

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