Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.

Oxidized low density lipoproteins cause contraction and inhibit endothelium-dependent relaxation in the pig coronary artery.
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氧化低密度脂蛋白引起猪冠状动脉收缩并抑制内皮依赖性舒张。

DOI:
10.1172/jci114718
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发表时间:
1990
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Cohen,RA
Cohen,RA
中科院分区:
--
文献类型:
--
作者:
Simon,BC;Cunningham,LD;Cohen,RA

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在猪右冠状动脉分离环中研究了天然低密度脂蛋白和氧化修饰低密度脂蛋白的直接血管活性作用及其对5-羟色胺内皮依赖性松弛的影响。缓慢发生的收缩是由天然低密度脂蛋白(100微克蛋白质/ml)引起的。在没有微量金属螯合剂EDTA存在的情况下,收缩更为明显,并且与反应过程中脂质过氧化物的形成相吻合。亲脂性抗氧化剂,丁基羟基甲苯,防止氧化和收缩,天然低密度脂蛋白。暴露于铜中氧化的低密度脂蛋白收缩冠状动脉的速度更快,阈值仅为1微克蛋白质/ml,但在100微克蛋白质/ml时具有类似的最大收缩。超氧化物歧化酶抑制天然低密度脂蛋白的收缩,而不抑制氧化低密度脂蛋白的收缩。过氧化氢酶阻断了天然和氧化低密度脂蛋白的收缩。对氧化低密度脂蛋白的收缩不受吲哚美辛的影响,但可以通过去除内皮或内皮源性松弛因子抑制剂来消除。氧化低密度脂蛋白而非天然低密度脂蛋白抑制内皮依赖的5-羟色胺松弛。因此,氧化的低密度脂蛋白引起由过氧化氢介导的内皮依赖性冠状动脉收缩。天然低密度脂蛋白的收缩是由于它们在器官腔内被超氧阴离子自由基氧化所致。氧化而非天然的低密度脂蛋白在体外损害正常内皮细胞血管扩张功能。氧化的低密度脂蛋白在动脉粥样硬化的发病机制中很重要,可能直接导致高胆固醇血症和动脉粥样硬化中血管痉挛的风险增加。
The direct vasoactive effects of native and oxidatively modified low density lipoproteins as well as their effects on endothelium-dependent relaxations to 5-hydroxytryptamine were studied in isolated rings of pig right coronary artery. Slowly developing contractions were caused by native low density lipoproteins (100 micrograms protein/ml). The contractions were more pronounced in the absence than in the presence of the trace metal chelator, EDTA, and coincided with the formation of lipid peroxides during the response. The lipophilic antioxidant, butylated hydroxytoluene, prevented the oxidation of, and contraction to, native low density lipoproteins. Low density lipoproteins oxidized by exposure to copper contracted coronary arteries more rapidly with a threshold of only 1 micrograms protein/ml, but with a similar maximal contraction at 100 micrograms protein/ml. Superoxide dismutase inhibited the contraction to native low density lipoproteins, but not to oxidized low density lipoproteins. Catalase blocked contractions to both native and oxidized low density lipoproteins. Contractions to oxidized low density lipoproteins were unaffected by indomethacin, but were abolished by removal of the endothelium or by inhibitors of endothelium-derived relaxing factor. Oxidized low density lipoproteins but not native low density lipoproteins inhibited endothelium-dependent relaxations to 5-hydroxytryptamine. Thus, oxidized low density lipoproteins caused endothelium-dependent coronary artery contractions which are mediated by a hydroperoxide. Contractions to native low density lipoproteins are due to their oxidation in the organ chamber by the superoxide anion radical. Oxidized, but not native, low density lipoproteins impair normal endothelial cell vasodilator function in vitro. Oxidized low density lipoproteins, important in the pathogenesis of atherosclerosis, may directly contribute to the increased risk of vasospasm seen in hypercholesterolemia and atherosclerosis.
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影响因子: 11.1
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影响因子: 15.9
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影响因子: --
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