Suppression of oxidative stress in endothelial progenitor cells promotes angiogenesis and improves cardiac function following myocardial infarction in diabetic mice.
Suppression of oxidative stress in endothelial progenitor cells promotes angiogenesis and improves cardiac function following myocardial infarction in diabetic mice.
复制标题
抑制内皮祖细胞氧化应激可促进血管生成并改善糖尿病小鼠心肌梗死后的心脏功能
DOI：
10.3892/etm.2016.3236
复制
发表时间：
2016-06
影响因子：
2.7
通讯作者：
Zhao Y
中科院分区：
文献类型：
--
作者：
Jin P;Li T;Li X;Shen X;Zhao Y
心肌梗死是糖尿病发病率和死亡率的主要因素，糖尿病缺血心脏血管生成不足和血液再灌注率低是糖尿病的主要特征。本研究旨在探讨内皮祖细胞(EPC)氧化应激对糖尿病小鼠心脏血管生成的影响。来自糖尿病小鼠的EPC显示，与正常小鼠相比，超氧化物歧化酶(SOD)的表达水平和活性降低。血管内皮管形成试验显示，与正常对照组相比，糖尿病内皮祖细胞的血管生成明显延迟。在糖尿病小鼠的心肌梗死模型中，接受了各种预处理的内皮细胞被测试为一种细胞疗法。过氧化氢或小干扰RNA介导的抑制超氧化物歧化酶基因敲除正常内皮祖细胞的氧化应激降低了它们在糖尿病小鼠缺血心肌中的血管生成活性。相反，对糖尿病小鼠的EPC进行细胞治疗，使其在SOD基因过表达后进行细胞治疗，或使用抗氧化剂Tempoll治疗，它们促进血管生成的能力正常。这些结果表明，EPC中SOD表达水平的降低导致了血管生成的受损。此外，通过体外超氧化物歧化酶基因治疗使糖尿病内皮祖细胞正常化，可加速内皮祖细胞促进血管生成和改善心功能的能力，将其用于糖尿病小鼠心肌梗死后的细胞治疗。
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 H2O2 or 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.