Oxidative enzymopathies and vascular disease
Oxidative enzymopathies and vascular disease
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DOI：
10.1161/01.atv.0000163846.51473.09
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发表时间：
2005-07-01
影响因子：
8.7
通讯作者：
Loscalzo, J
中科院分区：
文献类型：
--
作者：
Leopold, JA;Loscalzo, J
在脉管系统中，由线粒体呼吸和酶源产生的活性氧（ROS）作为细胞信号传导和稳态机制的组成部分。因为ROS是高度反应性的生物分子，所以细胞氧化还原环境由小分子抗氧化剂和抗氧化酶小心地维持，以防止ROS过量的有害后果。当这种氧化还原平衡受到干扰时，由于ROS产生增加或抗氧化能力降低，血管壁中的氧化应激增加，如果不抵消，则血管功能障碍加剧。已鉴定出许多促氧化酶的遗传多态性，包括5-脂氧合酶、环氧合酶-2、一氧化氮合酶-3和NAD（P）H氧化酶，并发现其调节ROS的产生，从而调节具有这些遗传多态性的个体患动脉粥样硬化血栓形成性心血管疾病的风险。类似地，抗氧化酶过氧化氢酶、谷胱甘肽过氧化物酶、谷胱甘肽-S-转移酶、血红素加氧酶和葡萄糖-6-磷酸脱氢酶的遗传性缺乏有利于ROS积累，并且与血管疾病的风险增加相关。单独地，这些多态性中的每一种都对脉管系统施加了未补偿的氧化应激状态，并且共同地包括氧化酶病。
In the vasculature, reactive oxygen species (ROS) generated by both mitochondrial respiration and enzymatic sources serve as integral components of cellular signaling and homeostatic mechanisms. Because ROS are highly reactive biomolecules, the cellular redox milieu is carefully maintained by small-molecule antioxidants and antioxidant enzymes to prevent the deleterious consequences of ROS excess. When this redox balance is perturbed, because of either increased ROS production or decreased antioxidant capacity, oxidant stress is increased in the vessel wall and, if not offset, vascular dysfunction ensues. A number of heritable polymorphisms of pro-oxidant enzymes, including 5-lipoxygenase, cyclooxygenase-2, nitric oxide synthase-3, and NAD(P) H oxidase, have been identified and found to modulate ROS production and, thereby, the risk of atherothrombotic cardiovascular disease in individuals with these genetic polymorphisms. Similarly, heritable deficiency of the antioxidant enzymes catalase, glutathione peroxidases, glutathione-S-transferases, heme oxygenase, and glucose-6-phosphate dehydrogenase favors ROS accumulation, and has been associated with an increased risk of vascular disease. Individually, each of these polymorphisms imposes a state of uncompensated oxidant stress on the vasculature and collectively comprise the oxidative enzymopathies.