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首页> 外文期刊>Cell biology international. >Diazoxide preconditioning of endothelial progenitor cells improves their ability to repair the infarcted myocardium
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Diazoxide preconditioning of endothelial progenitor cells improves their ability to repair the infarcted myocardium

机译：内皮祖细胞的二氮嗪预处理可改善其修复梗塞心肌的能力

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摘要

Reduced survival and homing of the transplanted cells in the oxidative stressed ischemic environment limits the potential outcome of cell therapies for myocardial ischemia. Diazoxide (DZ), a highly selective mitochondrial ATP sensitive K+ channel opener, is known to improve the survival and therapeutic ability of mesenchymal stem cells and skeletal myoblasts for the repair of heart failure. The current study explored the effect of DZ preconditioning in improving the ability of endothelial progenitor cells (EPCs) to counteract, in vitro oxidative stress, and to repair the infarcted myocardium. The EPCs were preconditioned by 30min incubation with 200M DZ followed by exposure to 200M hydrogen peroxide (H2O2) for 2h. Non-preconditioned EPCs with and without exposure to H2O2 were used as control. DZ preconditioning of EPCs resulted in significantly reduced cell injury as shown by reduced lactate dehydrogenase release and expression of annexin V-PE in comparison to untreated EPCs. Furthermore, DZ preconditioned EPCs exhibited upregulated expression of prosurvival genes (VEGF, SDF-1, PCNA, and Bcl(2)), improved chemokines release (VEGF, IGF, and SDF-1), viability, Akt phosphorylation and tube formation. In vivo experiments involved transplantation of DZ preconditioned and untreated EPCs in the left ventricle after permanent ligation of left anterior descending coronary artery in rats. The results demonstrated that DZ EPCs transplanted group showed significant reduction in infarct size along with robust cell proliferation, angiogenesis and improvement in cardiac function. The current study demonstrates that DZ preconditioning enhances EPCs survival under oxidative stress in vitro and their ability to treat myocardial infarction.
机译：在氧化应激的缺血性环境中，移植细胞的存活率降低和归巢降低，限制了细胞治疗心肌缺血的潜在结果。众所周知，Diazoxide（DZ）是一种高度选择性的线粒体ATP敏感K +通道开放剂，可改善间充质干细胞和骨骼肌成肌细胞的存活率和治疗心力衰竭的治疗能力。当前的研究探索了DZ预处理在提高内皮祖细胞（EPC）抵抗，体外氧化应激和修复梗塞心肌的能力方面的作用。通过与200M DZ孵育30分钟，然后将其暴露于200M过氧化氢（H2O2）中2h，对EPC进行预处理。暴露和不暴露于H2O2的未预处理EPC均用作对照。与未经处理的EPC相比，EZ的DZ预处理可显着减少细胞损伤，如乳酸脱氢酶释放减少和膜联蛋白V-PE的表达所表明。此外，DZ预处理的EPC表现出生存基因（VEGF，SDF-1，PCNA和Bcl（2））的表达上调，趋化因子释放（VEGF，IGF和SDF-1），活力，Akt磷酸化和管形成。体内实验涉及在大鼠左前降支冠状动脉永久结扎后在左心室中植入DZ预处理和未经处理的EPC。结果表明，DZ EPCs移植组的梗塞面积显着减少，同时细胞健壮增殖，血管生成和心脏功能改善。当前的研究表明，DZ预处理可提高EPC在体外氧化应激下的存活率及其治疗心肌梗塞的能力。

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