SUPEROXIDE AND PEROXYNITRITE IN ATHEROSCLEROSIS
SUPEROXIDE AND PEROXYNITRITE IN ATHEROSCLEROSIS
复制标题
DOI：
10.1073/pnas.91.3.1044
复制
发表时间：
1994-02-01
影响因子：
11.1
通讯作者：
TARPEY, MM
中科院分区：
文献类型：
--
作者：
WHITE, CR;BROCK, TA;TARPEY, MM
通过测试以下假设来检验活性氧在与动脉粥样硬化相关的血管病理学中的作用：一氧化氮 (.NO) 与超氧化物 (O2-) 反应产生氧化剂过氧亚硝酸盐 (ONOO-)，从而导致血管反应性受损。对喂食补充胆固醇饮食的兔子的股动脉进行收缩性研究。胆固醇喂养改变了乙酰胆碱 (ACh) 诱导的松弛的 EC50，并损害了对 ACh 的最大反应。我们使用 pH 敏感脂质体将 CuZn 超氧化物歧化酶（SOD；超氧化物：超氧化物氧化还原酶，EC 1.15.1.1）递送至 .NO 与 O2- 反应的关键位点。与对照组相比，静脉注射脂质体（每毫升 3000 单位 SOD）可以更大程度地增强胆固醇喂养组中乙酰胆碱诱导的松弛。定量免疫细胞化学证明 SOD 在内皮细胞和血管平滑肌细胞以及细胞外基质中的分布增强。脂质体处理的兔子血管匀浆中的 SOD 活性也有所增加。 β极低密度脂蛋白与ONOO-的孵育导致共轭二烯和硫代巴比妥酸反应物质的快速形成。我们的结果表明，O2- 与.NO 的反应通过产生有效的脂蛋白氧化介质以及通过限制.NO 对血管平滑肌鸟苷酸环化酶活性的刺激而参与动脉粥样硬化疾病的发展。
The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (.NO) with superoxide (O2-), yielding the oxidant peroxynitrite (ONOO-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of .NO reaction with O2-. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of beta very low density lipoprotein with ONOO- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O2- with .NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting .NO stimulation of vascular smooth muscle guanylate cyclase activity.