LIPOXYGENASE CONTRIBUTES TO THE OXIDATION OF LIPIDS IN HUMAN ATHEROSCLEROTIC PLAQUES
LIPOXYGENASE CONTRIBUTES TO THE OXIDATION OF LIPIDS IN HUMAN ATHEROSCLEROTIC PLAQUES
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DOI：
10.1172/jci118062
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发表时间：
1995-07-01
影响因子：
15.9
通讯作者：
CATHCART, MK
中科院分区：
文献类型：
--
作者：
FOLCIK, VA;NIVARARISTY, RA;CATHCART, MK
氧化的LDL存在于人类动脉粥样硬化病变中，但是负责体内氧化的机制尚未被明确证实，间接证据表明酶15-脂氧合酶是这种疾病中氧化脂质形成的贡献者，为了评估氧化脂质是否确实是通过15-脂氧合酶在体内对多不饱和脂肪酸（PUFA）的作用形成的，我们用了一种灵敏而特异的方法人15-脂氧合酶是一种ω-6脂氧合酶，其先前已显示以立体特异性方式氧化酯化PUFA，在LDL中由胆固醇亚油酸酯底物主要形成胆固醇过氧化氢-十八碳二烯酸酯（13（S）-HPODE）。这一性质使其活性区别于非酶氧化，非酶氧化导致相同氧化产物的等量S和R立体异构体的形成。共分析了80份人动脉粥样硬化斑块标本。从人动脉粥样硬化病变和铜氧化LDL中纯化了酯化、氧化亚油酸酯，比较了这些氧化产物的手性，发现人动脉粥样硬化病变中氧化亚油酸酯的氧化具有明显的立体特异性。在从人体病变中纯化的胆固醇酯衍生的HPODE中检测到更大的立体特异性。胆固醇HPODE是胆固醇亚油酸酯的主要氧化产物，胆固醇亚油酸酯是在动脉粥样硬化血管中积累的主要酯化PUFA，胆固醇HPODE及其还原形式胆固醇羟基十八碳二烯酸酯仅在所有分析的病变中检测到。无论是氧化的立体特异性，也没有可用的基板氧化的初级氧化产物的百分比与疾病的病变检查的阶段，我们的结论是，15-脂氧合酶有助于在人类动脉粥样硬化病变的氧化脂质的形成。
Oxidized LDL is present in human atherosclerotic lesions, but the mechanisms responsible for oxidation in vivo have not been definitively demonstrated, Circumstantial evidence has implicated the enzyme 15-lipoxygenase as a contributor to the formation of oxidized lipids in this disease, To assess whether oxidized lipids are indeed formed by the action of 15-lipoxygenase on polyunsaturated fatty acids (PUFAs) in vivo, we have used a sensitive and specific method (chiral phase HPLC) to analyze the lipid oxidation products present in human atherosclerotic lesions, Human 15-lipoxygenase is an omega-6 lipoxygenase that has previously been shown to oxidize esterified PUFA in a stereospecific manner, forming predominantly cholesteryl hydroperoxy-octadecadienoate (13(S)-HPODE) from cholesteryl linoleate substrate in LDL. This property allows its activity to be distinguished from nonenzymatic oxidation, which results in the Formation of equal quantities of the S and R stereoisomers of the same oxidation product, A total of 80 specimens of human atherosclerotic plaque were analyzed. Esterified, oxidized linoleate was purified from human atherosclerotic lesions and from LDL oxidized by copper, acid the chirality of these oxidation products was compared, There was significantly greater stereospecificity of oxidation in the oxidized linoleate from human atherosclerotic lesions. Even greater stereospecificity was detected in the HPODE derived from cholesteryl ester, purified from human lesions, Cholesteryl HPODE is the primary oxidation product from cholesteryl linoleate, the major esterified PUFA that accumulates in atherosclerotic vessels, Cholesteryl HPODE and its reduced form, cholesteryl hydroxy-octadecadienoate, mere detected in all lesions analyzed. Neither the stereospecificity of oxidation nor the percentage of available substrate oxidized to primary oxidation products was correlated with the stage of disease of the lesions examined, We conclude that 15-lipoxygenase contributes to the formation of oxidized lipids in human atherosclerotic lesions.