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

Shunji Hashizume; Masashi Akaike; Hiroyuki Azuma; Kazue Ishikawa; Sumiko Yoshida; Yuka Sumitomo-Ueda; Shusuke Yagi; Yasumasa Ikeda; Takashi Iwase; Ken-ichi Aihara; Masahiro Abe; Masataka Sata; Toshio Matsumoto

doi:10.5551/jat.5868

Original Article

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

Shunji Hashizume, Masashi Akaike, Hiroyuki Azuma, Kazue Ishikawa, Sumiko Yoshida, Yuka Sumitomo-Ueda, Shusuke Yagi, Yasumasa Ikeda, Takashi Iwase, Ken-ichi Aihara, Masahiro Abe, Masataka Sata, Toshio Matsumoto

Author information

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

Keywords: Platelet-derived growth factor, Peroxisome proliferator-activated receptor, Megakaryocytes, Platelets, Atherosclerosis

JOURNAL OPEN ACCESS

2011 Volume 18 Issue 2 Pages 138-147

DOI https://doi.org/10.5551/jat.5868

View "Advance Publication" version (November 2, 2010).

Details

Abstract

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.
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.
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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