Atorvastatin protects endothelial colony-forming cells against H(2)O(2)-induced oxidative damage by regulating the expression of annexin A2

Endothelial dysfunction and injury are central events in the pathogenesis of ischemic vascular disorders. Endothelial progenitor cells (EPCs) are mobilized from the bone marrow into the peripheral circulation, where they locate to sites of injured endothelium and are involved in endothelial repair and vascular regeneration. During these processes, EPCs are exposed to oxidative stress, a crucial pathological condition, which occurs during vascular injury and limits the efficacy of EPCs in the repair of injured endothelium. Statins are effective inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, and are commonly used to manage and prevent ischemic vascular disease by reducing plasma cholesterol levels. In addition to lowering cholesterol, statins have also been reported to exert pleiotropic actions, including anti-inflammatory and anti-oxidative activities. The present study aimed to investigate the ability of atorvastatin to protect endothelial colony-forming cells (ECFCs), a homogeneous subtype of EPCs, from hydrogen peroxide (H(2)O(2))-induced oxidative damage, and to determine the mechanism underlying this protective action. MTT assay, acridine orange/ethidium bromide staining, reactive oxygen species assay, western blot analysis and tube formation assay were employed. The results demonstrated that H(2)O(2) induced cell death and decreased the tube-forming ability of the ECFCs, in a concentration-dependent manner; however, these effects were partially attenuated following administration of atorvastatin. The reversion of the quantitative and qualitative impairment of the H(2)O(2)-treated ECFCs appeared to be mediated by the regulation of annexin A2, as the expression levels of annexin A2 were decreased following treatment with H(2)O(2) and increased following treatment with atorvastatin. These results indicated that annexin A2 may be involved in the H(2)O(2)-induced damage of ECFCs, and in the protective activities of atorvastatin in response to oxidative stress.