Department of Internal Medicine, University of Manitoba, 835-715 McDermot Avenue, Winnipeg MB R3E 3P4, Canada.
Can J Physiol Pharmacol. 2010 Mar;88(3):241-8. doi: 10.1139/Y10-018.
Cardiovascular diseases are the predominant cause of death in patients with diabetes mellitus. Underlying mechanism for the susceptibility of diabetic patients to cardiovascular diseases remains unclear. Elevated oxidative stress was detected in diabetic patients and in animal models of diabetes. Hyperglycemia, oxidatively modified atherogenic lipoproteins, and advanced glycation end products are linked to oxidative stress in diabetes. Mitochondria are one of major sources of reactive oxygen species (ROS) in cells. Mitochondrial dysfunction increases electron leak and the generation of ROS from the mitochondrial respiratory chain (MRC). High levels of glucose and lipids impair the activities of MRC complex enzymes. NADPH oxidase (NOX) generates superoxide from NADPH in cells. Increased NOX activity was detected in diabetic patients. Hyperglycemia and hyperlipidemia increased the expression of NOX in vascular endothelial cells. Accumulated lines of evidence indicate that oxidative stress induced by excessive ROS production is linked to many processes associated with diabetic cardiovascular complications. Overproduction of ROS resulting from mitochondrial dysfunction or NOX activation is associated with uncoupling of endothelial nitric oxide synthase, which leads to reduced production of nitric oxide and endothelial-dependent vasodilation. Gene silence or inhibitor of NOX reduced oxidized or glycated LDL-induced expression of plasminogen activator inhibitor-1 in endothelial cells. Statins, hypoglycemic agents, and exercise may reduce oxidative stress in diabetic patients through the reduction of NOX activity or the improvement of mitochondrial function, which may prevent or postpone the development of cardiovascular complications.
心血管疾病是糖尿病患者的主要死亡原因。糖尿病患者易患心血管疾病的潜在机制尚不清楚。在糖尿病患者和糖尿病动物模型中检测到氧化应激升高。高血糖、氧化修饰的动脉粥样硬化脂蛋白和糖基化终产物与糖尿病中的氧化应激有关。线粒体是细胞中活性氧（ROS）的主要来源之一。线粒体功能障碍增加了电子泄漏和线粒体呼吸链（MRC）产生 ROS 的能力。高浓度的葡萄糖和脂质会损害 MRC 复合物酶的活性。NADPH 氧化酶（NOX）在细胞中从 NADPH 产生超氧化物。在糖尿病患者中检测到 NOX 活性增加。高血糖和高血脂增加了血管内皮细胞中 NOX 的表达。越来越多的证据表明，过量 ROS 产生引起的氧化应激与许多与糖尿病心血管并发症相关的过程有关。线粒体功能障碍或 NOX 激活导致的 ROS 过度产生与内皮型一氧化氮合酶解偶联有关，导致一氧化氮产生减少和内皮依赖性血管舒张。NOX 的基因沉默或抑制剂可降低氧化或糖基化 LDL 诱导的内皮细胞纤溶酶原激活物抑制剂-1 的表达。他汀类药物、降糖药物和运动可通过降低 NOX 活性或改善线粒体功能来减少糖尿病患者的氧化应激，从而预防或延缓心血管并发症的发生。
