Abstract
PEDF is a highly effective endogenous inhibitor of angiogenesis. However, the pathophysiological role of PEDF in therapeutic angiogenesis in the setting of limb ischemia is not fully understood. In this study, we investigated whether inhibition of PEDF could augment vascular endothelial growth factor (VEGF)-induced therapeutic angiogenesis and blood flow recovery in ischemic hindlimbs of precocious-aging klotho mice. Adductor PEDF mRNA levels in nontreated mice were dramatically decreased at day 3 and 7 after ischemic surgery, whereas those in VEGF-treated mice were significantly increased after the surgery. VEGF treatment caused a progressive improvement of limb perfusion after induction of ischemia, which was augmented by the simultaneous treatment with anti-PEDF Ab. Further, PEDF administration was found to significantly impair the recovery of limb perfusion and post-ischemic angiogenesis in VEGF-treated mice. However, anti-PEDF Ab administration did not enhance the VEGF-induced increase in capillary number in ischemic adductor muscles. Our present study suggests that blockade of PEDF is a novel therapeutic strategy for limb ischemia, which could potentiate the beneficial effects of VEGF on therapeutic angiogenesis.
Keywords: PEDF, Post-ischemic angiogenesis, VEGF, PAD
Letters in Drug Design & Discovery
Title: Inhibition of Pigment Epithelium-Derived Factor (PEDF) Augments Vascular Endothelial Growth Factor (VEGF)-Induced Recovery of Limb Perfusion after Ischemia in Klotho Mouse
Volume: 7 Issue: 7
Author(s): Ken Arima, Sho-ichi Yamagishi, Takanori Matsui, Yutaka Saito, Yoshio Katsuki, Ken-ichiro Sasaki, Yousuke Katsuda, Hisashi Kai and Tsutomu Imaizumi
Affiliation:
Keywords: PEDF, Post-ischemic angiogenesis, VEGF, PAD
Abstract: PEDF is a highly effective endogenous inhibitor of angiogenesis. However, the pathophysiological role of PEDF in therapeutic angiogenesis in the setting of limb ischemia is not fully understood. In this study, we investigated whether inhibition of PEDF could augment vascular endothelial growth factor (VEGF)-induced therapeutic angiogenesis and blood flow recovery in ischemic hindlimbs of precocious-aging klotho mice. Adductor PEDF mRNA levels in nontreated mice were dramatically decreased at day 3 and 7 after ischemic surgery, whereas those in VEGF-treated mice were significantly increased after the surgery. VEGF treatment caused a progressive improvement of limb perfusion after induction of ischemia, which was augmented by the simultaneous treatment with anti-PEDF Ab. Further, PEDF administration was found to significantly impair the recovery of limb perfusion and post-ischemic angiogenesis in VEGF-treated mice. However, anti-PEDF Ab administration did not enhance the VEGF-induced increase in capillary number in ischemic adductor muscles. Our present study suggests that blockade of PEDF is a novel therapeutic strategy for limb ischemia, which could potentiate the beneficial effects of VEGF on therapeutic angiogenesis.
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Arima Ken, Yamagishi Sho-ichi, Matsui Takanori, Saito Yutaka, Katsuki Yoshio, Sasaki Ken-ichiro, Katsuda Yousuke, Kai Hisashi and Imaizumi Tsutomu, Inhibition of Pigment Epithelium-Derived Factor (PEDF) Augments Vascular Endothelial Growth Factor (VEGF)-Induced Recovery of Limb Perfusion after Ischemia in Klotho Mouse, Letters in Drug Design & Discovery 2010; 7 (7) . https://dx.doi.org/10.2174/157018010791526313
DOI https://dx.doi.org/10.2174/157018010791526313 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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