Li Ting-Bo, Zhang Jie-Jie, Liu Bin, Luo Xiu-Ju, Ma Qi-Lin, Peng Jun
a Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410078, China.
b Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha 410013, China.
Can J Physiol Pharmacol. 2017 May;95(5):474-480. doi: 10.1139/cjpp-2016-0142. Epub 2016 Oct 20.
NADPH oxidase (NOX) is a major source of reactive oxygen species (ROS) in the body and it plays a key role in mediation of oxidative injury in the cardiovascular system. The purposes of this study are to evaluate the status of NOX in endothelial progenitor cells (EPCs) of hyperlipidemic rats and to determine whether NOX-derived ROS promotes the dysfunction of EPCs. The rats were fed on a high-fat diet for 8 weeks to establish a hyperlipidemic rat model, which showed the increased plasma lipids and the impaired functions of circulating EPCs (including the reduced abilities in migration and adhesion) accompanied by an increase in NOX activity and ROS production. Next, EPCs were isolated from normal rats and they were treated with oxidized low-density lipoprotein (ox-LDL) (100 μg/mL) for 24 h to induce a dysfunctional model in vitro. In agreement with our findings in vivo, ox-LDL treatment increased the dysfunctions of EPCs concomitant with an increase in NOX activity and ROS production; these phenomena were reversed by the NOX inhibitor. Based on these observations, we conclude that NOX-derived ROS involved in the dysfunctions of circulating EPCs in hyperlipidemic rats and inhibition of NOX might provide a novel strategy to improve EPC functions in hyperlipidemia.
NADPH氧化酶（NOX）是体内活性氧（ROS）的主要来源，在介导心血管系统氧化损伤中起关键作用。本研究的目的是评估高脂血症大鼠内皮祖细胞（EPCs）中NOX的状态，并确定NOX衍生的ROS是否促进EPCs功能障碍。将大鼠喂食高脂饮食8周以建立高脂血症大鼠模型，该模型显示血浆脂质增加，循环EPCs功能受损（包括迁移和粘附能力降低），同时伴有NOX活性和ROS产生增加。接下来，从正常大鼠中分离出EPCs，并用氧化低密度脂蛋白（ox-LDL）（100μg/mL）处理24小时以在体外诱导功能障碍模型。与我们在体内的发现一致，ox-LDL处理增加了EPCs的功能障碍，同时NOX活性和ROS产生增加；这些现象被NOX抑制剂逆转。基于这些观察结果，我们得出结论，NOX衍生的ROS参与高脂血症大鼠循环EPCs的功能障碍，抑制NOX可能为改善高脂血症中EPCs功能提供一种新策略。
