VEGF-C regulates lymphangiogenesis and capillary stability by regulation of PDGF-B

Mitsuho Onimaru, Yoshikazu Yonemitsu, Takaaki Fujii, Mitsugu Tanii, Toshiaki Nakano, Kazunori Nakagawa, Ri Ichiro Kohno, Mamoru Hasegawa, Shin Ichi Nishikawa, Katsuo Sueishi

研究成果: ジャーナルへの寄稿学術誌査読

39 被引用数 (Scopus)

抄録

Emerging evidence indicates that the tight communication between vascular endothelial cells and mural cells using platelet-derived growth factor (PDGF)-BB is essential for capillary stabilization during the angiogenic process. However, little is known about the related regulator that determines PDGF-BB expression. Using murine models of therapeutic neovascularization, we here show that a typical lymphangiogenic factor, vascular endothelial growth factor (VEGF)-C, is an essential regulator determining PDGF-BB expression for vascular stabilization via a paracrine mode of action. The blockade of VEGF type 3 receptor (VEGFR3) using neutralizing antibody AFL-4 abrogated FGF-2-mediated limb salvage and blood flow recovery in severely ischemic hindlimb. Interestingly, inhibition of VEGFR3 activity not only diminished lymphangiogenesis, but induced marked dilatation of capillary vessels, showing mural cell dissociation. In these mice, VEGF-C and PDGF-B were upregulated in the later phase after induced ischemia, on day 7, when exogenous FGF-2 expression had already declined, and blockade of VEGFR3 or PDGF-BB activities diminished PDGF-B or VEGF-C expression, respectively. These results clearly indicate that VEGF-C is a critical mediator, not only for lymphangiogenesis, but also for capillary stabilization, the essential molecular mechanism of communication between endothelial cells and mural cells during neovascularization.

本文言語英語
ページ(範囲)H1685-H1696
ジャーナルAmerican Journal of Physiology - Heart and Circulatory Physiology
297
5
DOI
出版ステータス出版済み - 11月 2009

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 循環器および心血管医学
  • 生理学(医学)

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