Glycoxidative stress and cardiovascular complications in experimentally-induced diabetes: effects of antioxidant treatment.
Glycoxidative stress and cardiovascular complications in experimentally-induced diabetes: effects of antioxidant treatment.
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DOI：
10.2174/1874192401004010240
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发表时间：
2010-11-26
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影响因子：
--
通讯作者：
Karasu C
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作者：
Karasu C
糖尿病（DM）是一种常见的代谢性疾病，是冠心病、外周动脉疾病和高血压等心血管并发症发生的严重危险因素。氧化应激 (OS) 是 DM 的一个特征，被定义为活性氧 (ROS) 稳态水平的增加，可能是由于自由基生成增加和/或抗氧化防御机制减少而发生。越来越多的证据表明，高血糖是糖尿病组织损伤的始因，要么是通过细胞葡萄糖代谢的反复急性变化，要么是通过糖化生物分子和晚期糖基化终产物 (AGE) 的长期积累。 AGE 是通过美拉德过程形成的，这是葡萄糖分子的酮基或醛与蛋白质的氨基之间的非酶促反应，导致蛋白质老化和 DM 的病理并发症。在不受控制的高血糖情况下，AGEs和脂质过氧化产物的形成增加，加剧细胞内OS，导致分子完整性丧失、细胞信号传导和体内平衡破坏，进而导致炎症和组织损伤，如内皮功能障碍、动脉硬化和微血管并发症。除了 AGE 产生增加外，还有证据表明多种途径可提高 DM 中 ROS 的产生，包括：增强葡萄糖自动氧化、增加线粒体超氧化物产生、NADPH 氧化酶的蛋白激酶 C 依赖性激活、解偶联内皮一氧化氮合酶 (eNOS) 活性、增加通过多元醇途径的底物通量以及刺激类二十烷酸代谢。因此，纠正这些变量可以改善糖尿病心血管异常也就不足为奇了。这些现象之间的一个联系因素是糖氧化应激（GOS）导致的细胞氧化还原失衡。因此，最近的兴趣集中在预防、逆转或延迟 GOS 的策略上，以改变糖尿病心血管异常的自然史。本综述将讨论 GOS 与糖尿病引起的心血管疾病之间的联系，以及抗氧化疗法对改变糖尿病动物模型心血管并发症发展的作用。
Diabetes mellitus (DM) is a common metabolic disease, representing a serious risk factor for the development of cardiovascular complications, such as coronary heart disease, peripheral arterial disease and hypertension. Oxidative stress (OS), a feature of DM, is defined as an increase in the steady-state levels of reactive oxygen species (ROS) and may occur as a result of increased free radical generation and/or decreased anti-oxidant defense mechanisms. Increasing evidence indicates that hyperglycemia is the initiating cause of the tissue damage in DM, either through repeated acute changes in cellular glucose metabolism, or through long-term accumulation of glycated biomolecules and advanced glycation end products (AGEs). AGEs are formed by the Maillard process, a non-enzymatic reaction between ketone group of the glucose molecule or aldehydes and the amino groups of proteins that contributes to the aging of proteins and to the pathological complications of DM. In the presence of uncontrolled hyperglycemia, the increased formation of AGEs and lipid peroxidation products exacerbate intracellular OS and results in a loss of molecular integrity, disruption in cellular signaling and homeostasis, followed by inflammation and tissue injury such as endothelium dysfunction, arterial stiffening and microvascular complications. In addition to increased AGE production, there is also evidence of multiple pathways elevating ROS generation in DM, including; enhanced glucose auto-oxidation, increased mitochondrial superoxide production, protein kinase C-dependent activation of NADPH oxidase, uncoupled endothelial nitric oxide synthase (eNOS) activity, increased substrate flux through the polyol pathway and stimulation of eicosanoid metabolism. It is, therefore, not surprising that the correction of these variables can result in amelioration of diabetic cardiovascular abnormalities. A linking element between these phenomena is cellular redox imbalance due to glycoxidative stress (GOS). Thus, recent interest has focused on strategies to prevent, reverse or retard GOS in order to modify the natural history of diabetic cardiovascular abnormalities. This review will discuss the links between GOS and diabetes-induced cardiovascular disorders and the effect of antioxidant therapy on altering the development of cardiovascular complications in diabetic animal models.