Effects of Arginine on Endothelial Progenitor Cell Mobilization in Obese Mice Subjected to Limb Ischemia

Obesity is a worldwide health problem that is associated with many metabolic disorders including cardiovascular diseases, hypertension, diabetes, stroke etc. Vascular endothelial dysfunction accompanied by an up-regulated inflammatory reaction occur in obesity may contribute to atherosclerosis, distal limb ischemia and amputation. Bone marrow-derived endothelial progenitor cells (EPCs) constitute a reparative response to ischemic injury. EPCs have been shown to be involved in neovascularization, wound healing, tissue regeneration, and tissue remodeling. Previous studies reported that chronic inflammation and oxidative stress as observed in obesity impaired the normal physiology of EPC mobilization. Hypoxia-inducible factor (HIF)-1 is an oxygendependent transcriptional activator, which plays important roles in the angiogenesis of ischemic tissues. HIF-1α is necessary for the expressions of vascular endothelial growth factor (VEGF) and stromal cell-derived factor (SDF)-1. These factors promote the secretion of endothelial nitric oxide (NO) and enhance the mobilization of EPC. Arginine (Arg) is a non-essential amino acid. It is the precursor of NO. Previous studies showed that Arg has anti-inflammatory and anti-oxidative effects on catabolic conditions. Arg was also found to have protective effects on ischemia/reperfusioninduced tissue injury possibly via Arg-NO pathway. Since NO plays important role in the mobilization of EPC, some studies investigated the bioavailability of NO on the alteration of EPC. However, no study investigated the effect of dietary Arg supplementation on the changes of EPC under limb ischemia in obese mice. The results of this study may provide basic information for the clinical application of Arg in obese patients with critical limb ischemia.