Period2 deficiency blunts hypoxia-induced mobilization and function of endothelial progenitor cells

Abstract

Background: In the clinic, variations in circadian rhythm are evident in patients with cardiovascular disease, and the risk of cardiovascular events increases when rhythms are disrupted. In this study, we focused on the role of the circadian gene period! (per2) in mobilization and function of endothelial progenitor cells (EPCs) in vitro and in vivo after myocardial infarction (Ml) in mice. Methods and Results: Ml was produced by surgical ligation of the left anterior descending coronary artery in mice with and without per2 deficiency. Trans-thoraclc echocardiography was used to evaluate cardiac function in mice. Per2-/- mice with Ml showed decreased cardiac function and increased infarct size. The number of CD34+ cells and capillary density were decreased in the myocardium of per2-/- mice on immunohistochemistry. Flow cytometry revealed decreased number of circulating EPCs in per2-/- mice after Ml. In vitro, per2-/- EPCs showed decreased migration and tube formation capacity under hypoxia. Western blot analysis revealed inhibited activation of extracellular signal-regulated kinase and Akt signaling in the bone marrow of per2-/- mice and inhibited P13K/Akt expression in per2-/- EPCs under hypoxia. Conclusions: Per2 modulates EPC mobilization and function after Ml, which is important to recovery after Ml in mice.