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.
Export Options
About this article
Cite this article as:
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Potential Anticancer Properties of Bisphosphonates: Insights From Preclinical Studies
Anti-Cancer Agents in Medicinal Chemistry Anticancer Mechanisms of Berberine: A Good Choice for Glioblastoma Multiforme Therapy
Current Medicinal Chemistry New Hybrids with 2-aminobenzothiazole and Azelayl Scaffolds: Synthesis, Molecular Docking and Biological Evaluation
Current Organic Chemistry Cytotoxicity of a Vanadyl(IV) Complex with a Multidentate Oxygen Donor in Osteoblast Cell Lines in Culture
Medicinal Chemistry Craniofacial Fibrous Dysplasia Involvements of Mccune-Albright Syndrome: A Review with an Additional Case
Current Medical Imaging “Metabolic Reprogramming” in Ovarian Cancer Cells Resistant to Cisplatin
Current Cancer Drug Targets Long Non-Coding RNA GAS5 in Age-Related Diseases
Current Medicinal Chemistry Sida cordifolia, a Traditional Herb in Modern Perspective – A Review
Current Traditional Medicine The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development
Current Molecular Medicine Marine Natural Products and Related Compounds as Anticancer Agents: an Overview of their Clinical Status
Anti-Cancer Agents in Medicinal Chemistry Clinical Applications and Biosafety of Human Adult Mesenchymal Stem Cells
Current Pharmaceutical Design Targeted Therapy of the Insulin-Like Growth Factor-1 Receptor in Cancer
Combinatorial Chemistry & High Throughput Screening Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and Telomerase in Cancer Therapy
Current Pharmaceutical Design Classification of Sarcomas Using Bioinformatics and Molecular Profiling
Current Pharmaceutical Biotechnology Human Reduced Folate Carrier Gene and Transcript Variants: Functional, Physiologic, and Pharmacologic Consequences
Current Pharmacogenomics Anti-Tumour Effects of Bisphosphonates - What have we Learned from In Vivo Models?
Current Cancer Drug Targets Emerging Strategies and Challenges for Controlled Delivery of Taxanes: A Comprehensive Review
Current Drug Metabolism Piper Sarmentosum: A New Hope for the Treatment of Osteoporosis
Current Drug Targets Nitrosative Stress as a Mediator of Apoptosis: Implications for Cancer Therapy
Current Pharmaceutical Design Chromatin Remodeling Agents for Cancer Therapy
Reviews on Recent Clinical Trials