Authors: Uchida, C.; Haas, T. L.

Source: Current Pharmaceutical Design, Volume 15, Number 4, February 2009 , pp. 411-421(11)

Publisher: Bentham Science Publishers

Abstract:

Peripheral artery disease is characterized by reduced blood flow to the lower limb, resulting in chronic ischemia in these muscles, which can lead to eventual amputation of the affected limb. Stimulation of angiogenesis in the ischemic region would be of therapeutic benefit; however, attempts to increase angiogenesis through delivery of vascular endothelial growth factor (VEGF) largely have been unsuccessful. Recent studies have shown that VEGF signaling through its receptors, VEGFR1 and VEGFR2, is much more complex than previously appreciated. This review will examine current research into the function of VEGFR1 and -2 signaling pathways, and evidence of cross-talk between these two receptors. The potential impact of endothelial cell co-stimulation via other growth factors/cell surface receptors (such as angiopoietins and ephrins) on angiogenesis also will be discussed. Evidence suggesting deficiencies in VEGF pathway signaling in individuals with chronic ischemia and diabetes will be discussed. Numerous pro-angiogenic therapies for ischemia have been employed. The successes and limitations of these therapies will be illustrated, emphasizing more recent angiogenesis therapies that focus on activating co-ordinated patterns of pro-angiogenic genes as the most promising direction in the treatment of ischemic muscle tissue in peripheral artery disease.

Keywords: Angiogenesis; VEGF signaling; VEGF receptors; ischemia; diabetes; therapies

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138161209787315800

Affiliations: 1: School of Kinesiology and Health Science, Rm. 341 Farquharson, York University, 4700 Keele St., Toronto, ON, Canada, M3J 1P3.

Publication date: 2009-02-01

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• Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.
  
  Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.

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