Time course effect of hypoxia on bone marrow-derived endothelial progenitor cells and their effects on left ventricular function after transplanted into acute myocardial ischemia rat

摘要

OBJECTIVE: Ischemic heart disease is the most common cause of cardiovascular morbidity and mortality in the industrialized world, and the incidence has been increasing in developing countries. Stem cell transplantation has emerged as a potent new therapeutic strategy for acute/chronic ischemic heart disease and has been explored extensively. The present study aimed to investigate whether hypoxic preconditioning of endothelial progenitor cells (EPCs) before transplantation could ameliorate their survival and engraftment in ischemic tissue and the potential mechanisms. MATERIALS AND METHODS: EPCs extracted were subjected to increasing hypoxia for 24-72 h, survival and function of the preconditioned EPCs were assayed in both in vitro and in vivo. RESULTS: Hypoxia for 24 h caused significant enhancements in formation of tube like structure and motility of BM-EPCs (p < 0.05), as well as mRNA expressions of CXCR4, PI3K, AKT, and NF-κB, while these effects were reversed by prolonged hypoxia (48 and 72 h, p < 0.05). Hypoxia of BM-EPCs for 24 h did not result in increased apoptosis resistance, and cell apoptosis was even enhanced by prolonged hypoxia. In vivo transplantation experiments demonstrated the beneficial effect of hypoxic EPCs on left ventricular (LV) functions after acute myocardial ischemia (AMI). CONCLUSIONS: Shorter-term hypoxia showed better survival, differentiation and function of BM-EPCs in vivo, further study was still needed to optimize the hypoxic pattern of BM-EPCs so as to better protect heart from myocardial ischemic injury. The present study showed evidence suggested that hypoxic preconditioning did exert further beneficial effects of BM-EPCs on preservation of LV function after AMI. Short-term exposure to hypoxia for about 24 h provided better condition for survival and function of BM-EPCs.