CHOLESTERYL ESTER SYNTHESIS IN NORMAL AND ATHEROSCLEROTIC AORTAS OF RABBITS AND RHESUS-MONKEYS
CHOLESTERYL ESTER SYNTHESIS IN NORMAL AND ATHEROSCLEROTIC AORTAS OF RABBITS AND RHESUS-MONKEYS
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DOI：
10.1161/01.res.35.5.692
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发表时间：
1974-01-01
影响因子：
20.1
通讯作者：
CHOBANIAN, AV
中科院分区：
文献类型：
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作者：
BRECHER, PI;CHOBANIAN, AV
使用来自正常和动脉粥样硬化兔和恒河猴主动脉的亚细胞级分研究了主动脉组织中胆固醇酯的形成。研究了两种能够在体外将 1-14C-油酸酯化为胆固醇酯的酶系统的特性，并且证明了两种系统的活性因胆固醇喂养而增加。使用微粒体制剂来研究 ATP、CoA 依赖性酯化，该酯化涉及两种酶：脂肪酰基 CoA 合成酶和脂肪酰基 CoA：胆固醇酰基转移酶。对这两种酶的特性进行了研究，结果表明，由于 3-6 个月的胆固醇喂养，主动脉微粒体中丙烯酰基转移酶的活性增加了约四倍。还观察到在酸性pH下主动脉高速上清液部分将油酸酯化为胆固醇酯；所涉及的酶系统不需要辅因子，并且其活性由于胆固醇喂养而大大增加。当比较正常和动脉粥样硬化恒河猴主动脉部分时，发现两种酯化酶系统的活性类似增加。对氯苯氧基异丁酸酯（CPIB）和2-甲基-2-[对-（1,2,3,4-四氢-1-萘基）-苯氧基]丙酸（TPIA）对两种胆固醇酯化酶系统产生抑制作用。对于两种酶系统，TPIA 都是比 CPIB 更有效的抑制剂，效果至少高一个数量级。这些研究表明，主动脉组织细胞内胆固醇酯合成的增加可能有助于其在动脉粥样硬化中的积累。
The formation of cholesteryl ester in aortic tissue was studied using subcellular fractions from normal and atherosclerotic rabbit and rhesus monkey aortas. The properties of two enzyme systems capable of esterifying 1-14C-oleic acid into cholesteryl ester in vitro were investigated, and increased activity was demonstrated for both systems as a result of cholesterol feeding. Microsomal preparations were used to study the ATP, CoA-dependent esterification which involves two enzymes, fatty acyl CoA synthetase and fatty acyl CoA: cholesterol acyltransferase. The properties of both enzymes were investigated, and an increase of about fourfold in activity of the acryltransfrease was demonstrated in aortic microsomes as a result of cholesterol feeding for 3-6 months. Esterification of oleic acid into cholesteryl ester by aortic high-speed supernatant fractions at an acidic pH was also observed; the enzyme system involved did not require cofactors, and its activity greatly increased as a result of cholesterol feeding. Similar increases in the activity of both esterifying enzyme systems were found when normal and atherosclerotic rhesus monkey aortic fractions were compared.p-Chlorophenoxyisobutyrate (CPIB) and 2-methyl-2-[p-(1, 2, 3, 4-tetrahydro-l-naphthyl)-phenoxy]propionic acid (TPIA) produced inhibition of both cholesterol-esterifying enzyme systems. TPIA was a more effective inhibitor than CPIB on both enzyme systems by at least an order of magnitude. These studies suggest that increased intracellular synthesis of cholesteryl ester by aortic tissue may contribute to its accumulation in atherosclerosis.