In the Western world, peripheral vascular disease (PVD) has a high prevalence with high morbidity and mortality. In a large percentage of these patients, lower limb amputation is still required. Studies of ischaemic skeletal muscle disclosed evidence of endogenous angiogenesis and adaptive skeletal muscle metabolic changes in response to hypoxia. Chemokines are potent chemoattractant cytokines that regulate leukocyte trafficking in homeostatic and inflammatory processes. More than 50 different chemokines and 20 different chemokine receptors have been cloned. The chemokine stromal-cell-derived factor-1 (SDF-1 aka CXCL12) is a constitutively expressed and inducible chemokine that regulates multiple physiological processes, including embryonic development and organ homeostasis. The biologic effects of SDF-1 are mediated by chemokine receptor CXCR4, a 352 amino acid rhodopsin-like transmembrane-specific G protein-coupled receptor (GPCR). There is evidence that the administration of SDF-1 increases blood flow and perfusion via recruitment of endothelial progenitor cells (EPCs). This review will focus on the role of the SDF-1/CXCR4 system in the pathophysiology of PVD and discuss their potential as therapeutic targets for PVD. 1. Introduction Atherosclerotic peripheral vascular disease (PVD) is a major cause of morbidity and mortality in the Western world [1]. It has been reported to have 19.1% prevalence in those over 55 years of age [2], and 15% of male patients die within 5 years of diagnosis, with the deaths mostly due to other associated atherosclerotic disease such as stroke, coronary heart disease, and abdominal vascular disease [3]. With an aging population and improved medical care that has increased life expectancy, more patients are presenting with critical leg ischemia (CLI), the end stage of PVD. In 10 to 40% of these patients [4], lower limb amputation may be required because the anatomic extent and the distribution of arterial occlusive disease make the patients unsuitable for revascularization, despite current advances in surgery and endovascular revascularization techniques. In the past 20 years, rapid development in molecular biology and understanding of mechanisms of angiogenesis [5] have led to the development of therapeutic angiogenesis as a promising strategy to treat a variety of cardiovascular diseases. Experimental animal model studies [6] have progressed to several clinical trials which evaluated the angiogenic potentials of growth factors such as hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), and
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