Koulis C, Watson A M D, Gray S P, Jandeleit-Dahm K A
Diabetic Complications Division, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Central Clinical School, Department of Medicine, Monash University, Melbourne, Australia.
Diabetic Complications Division, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia; Central Clinical School, Department of Medicine, Monash University, Melbourne, Australia.
Diabetes Metab. 2015 Sep;41(4):272-281. doi: 10.1016/j.diabet.2015.01.006. Epub 2015 Aug 29.
Diabetes-associated micro- and macrovascular complications contribute to the increased morbidity and mortality observed in diabetes. Diabetes leads to accelerated generation of advanced glycation end products (AGEs) and activation of their receptor, RAGE, as well as activation of NAD(P)H oxidase (Nox), an enzyme dedicated to the production of reactive oxygen species, which ultimately leads to a pro-inflammatory environment characterised by oxidative stress. This review outlines the current evidence about the contribution of and interaction between the AGE-RAGE axis and Nox derived ROS formation in the development and progression of micro- and macrovascular diabetic complications (especially in atherosclerosis and nephropathy), and the mechanisms by which this occurs. We also outline novel treatments targeting the AGE-RAGE axis and specific Nox isoforms, which hold great promise in attenuating the development of diabetes-associated atherosclerosis and diabetic nephropathy.
糖尿病相关的微血管和大血管并发症导致了糖尿病患者中观察到的发病率和死亡率的增加。糖尿病会加速晚期糖基化终末产物（AGEs）的生成及其受体RAGE的激活，以及NAD(P)H氧化酶（Nox）的激活，Nox是一种专门产生活性氧的酶，最终导致以氧化应激为特征的促炎环境。本综述概述了目前关于AGE-RAGE轴与Nox衍生的活性氧形成在微血管和大血管糖尿病并发症（尤其是动脉粥样硬化和肾病）的发生和发展中的作用及相互作用的证据，以及其发生的机制。我们还概述了针对AGE-RAGE轴和特定Nox亚型的新型治疗方法，这些方法在减轻糖尿病相关动脉粥样硬化和糖尿病肾病的发展方面具有很大的前景。
