Pigment-epithelium-derived factor (PEDF) inhibits angiotensin-II-induced vascular endothelial growth factor (VEGF) expression in MOLT-3 T cells through anti-oxidative properties

Sho ichi Yamagishi, Takanori Matsui, Kazuo Nakamura, Takafumi Yoshida, Kyoko Shimizu, Yoshiaki Takegami, Tadamichi Shimizu, Hiroyoshi Inoue, Tsutomu Imaizumi

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Angiotensin II (Ang II), the dominant effector of the renin-angiotensin system, elicits numerous inflammatory-proliferative responses, thereby being involved in angiogenesis. T cells play an important role in angiogenesis as well by delivering vascular endothelial growth factor (VEGF) to inflammatory sites. Since we have previously shown that pigment-epithelium-derived factor (PEDF) blocks the Ang II signaling in endothelial cells, we studied here whether PEDF could inhibit the Ang-II-induced VEGF expression in MOLT-3 T and examined the potential mechanism of PEDF inhibitory effects. Ang II significantly up-regulated VEGF mRNA levels in MOLT-3 T cells, which was inhibited by PEDF or olmesartan, an Ang II type 1 receptor blocker. PEDF blocked the Ang-II-induced reactive oxygen species (ROS) generation in MOLT-3 T cells. Furthermore, H2O2 was found to up-regulate VEGF mRNA levels in MOLT-3 T cells in a dose-dependent manner. These results demonstrate that PEDF could inhibit the Ang-II-induced VEGF expression in MOLT-3 T cells via suppression of ROS generation. Blockade by PEDF of VEGF expression in T cells may become a novel therapeutic target for pathological angiogenesis.

Original languageEnglish
Pages (from-to)222-226
Number of pages5
JournalMicrovascular Research
Volume71
Issue number3
DOIs
Publication statusPublished - 2006 May 1
Externally publishedYes

Keywords

  • Angiogenesis
  • Angiotensin II
  • PEDF
  • ROS

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology

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