【2022年1月締切】CiNii ArticlesへのCiNii Researchへの統合に伴う機関認証の移行確認について

【1/6更新】2022年4月1日からのCiNii ArticlesのCiNii Researchへの統合について

Activation of Peroxisome Proliferator-Activated Receptor α in Megakaryocytes Reduces Platelet-Derived Growth Factor-BB in Platelets

  • Hashizume Shunji
    Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences.
  • Akaike Masashi
    Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences.
  • Azuma Hiroyuki
    Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences.
  • Ishikawa Kazue
    Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences.
  • Yoshida Sumiko
    Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences.
  • Sumitomo-Ueda Yuka
    Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences.
  • Yagi Shusuke
    Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences.
  • Ikeda Yasumasa
    Department of Pharmacology, The University of Tokushima Graduate School of Health Biosciences.
  • Iwase Takashi
    Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences.
  • Aihara Ken-ichi
    Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences.
  • Abe Masahiro
    Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences.
  • Sata Masataka
    Department of Cardiovascular Medicine, The University of Tokushima Graduate School of Health Biosciences.
  • Matsumoto Toshio
    Department of Medicine and Bioregulatory Sciences, The University of Tokushima Graduate School of Health Biosciences.

抄録

Aim: Platelet-derived growth factor (PDGF)-BB plays a crucial role in atherosclerosis and vascular remodeling by promoting the migration and proliferation of vascular smooth muscle cells. The objective of this study was to clarify the pleiotropic effect of peroxisome proliferator-activated receptor α (PPARα) activators on PDGF-BB expression in megakaryocytes and platelets.<BR>Methods and Results: The expression of PPARα in a human erythroleukemia (HEL) cells was clearly detected by reverse transcriptase-PCR and immunofluorescence microscopy. The expression level of PPARα in HEL cells was unchanged regardless of differentiation into megakaryocytic cells by treatment with phorbol 12-myristate 13 acetate (TPA). The TPA-induced expression of PDGF-B mRNA and PDGF-BB protein levels in culture media was significantly decreased by treatment with PPARα activators, Wy14643 and fenofibric acid, in a dose-dependent manner. PDGF-BB expression induced by inflammatory cytokines, including interleukin-1β or interleukin-6, was also significantly suppressed by treatment with PPARα activators. Immunohistochemistry of human bone marrow showed the expression of PPARα in both the nucleus and cytoplasm of megakaryocytes. In addition, PDGF-BB levels in platelets were significantly decreased from 1,800±870 to 1,470±840 pg/105 platelets (mean±SD, p<0.05) by treatment with 300 mg fenofibrate once daily for 4 weeks in 13 patients with dyslipidemia.<BR>Conclusions: Activation of PPARα in megakaryocytes reduces PDGF-BB expression in platelets. PPARα activators may exert vasculo-protective action through suppression of PDGF-BB production in a megakaryocyte/platelet pathway.

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