Suppression of oxidative stress in endothelial progenitor cells promotes angiogenesis and improves cardiac function following myocardial infarction in diabetic mice.
Myocardial infarction is a major contributor to morbidity and mortality in diabetes, which is characterized by inadequate angiogenesis and consequent poor blood reperfusion in the diabetic ischemic heart. The aim of the present study was to investigate the effect that oxidative stress in endothelial progenitor cells (EPCs) has on cardiac angiogenesis in diabetic mice. EPCs derived from diabetic mice revealed reductions in superoxide dismutase (SOD) expression levels and activity compared with those from normal mice. An endothelial tube formation assay showed that angiogenesis was markedly delayed for diabetic EPCs, compared with normal controls. EPCs subjected to various pretreatments were tested as a cell therapy in a diabetic mouse model of myocardial infarction. Induction of oxidative stress in normal EPCs by H2O2or small interfering RNA-mediated knockdown of SOD reduced their angiogenic activity in the ischemic myocardium of the diabetic mice. Conversely, cell therapy using EPCs from diabetic mice following SOD gene overexpression or treatment with the antioxidant Tempol normalized their ability to promote angiogenesis. These results indicate that decreased expression levels of SOD in EPCs contribute to impaired angiogenesis. In addition, normalization of diabetic EPCs by ex vivo SOD gene therapy accelerates the ability of the EPCs to promote angiogenesis and improve cardiac function when used as a cell therapy following myocardial infarction in diabetic mice.
Cardiovascular Center, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Peng
P
Jin
Cardiovascular Center, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Tao
T
Li
Cardiovascular Center, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Xueqi
X
Li
Cardiovascular Center, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Xinghua
X
Shen
Cardiovascular Center, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Yanru
Y
Zhao
angiogenesis; diabetes; endothelial progenitor cells; myocardial infarction; superoxide dismutase