Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1.
Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1.
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发表时间：
2000-09
影响因子：
6.5
通讯作者：
M. Navab;S. Hama;C. Cooke;G. Anantharamaiah;M. Chaddha;Linda Jin;G. Subbanagounder;Kim F. Faull;S. T. Reddy;Norman E. Miller;A. Fogelman
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作者：
M. Navab;S. Hama;C. Cooke;G. Anantharamaiah;M. Chaddha;Linda Jin;G. Subbanagounder;Kim F. Faull;S. T. Reddy;Norman E. Miller;A. Fogelman
载脂蛋白A-I(apoA-I)和一个apoA-I多肽模拟物去除了人低密度脂蛋白(LDL)中的种子分子，使其对人动脉壁细胞的氧化具有抵抗力。ApoA-I相关的种子分子包括氢过氧十八碳二烯酸(HPODE)和氢过氧二十碳四烯酸(HPETE)。遗传易感于脂肪条纹病变形成的小鼠的低密度脂蛋白对动脉壁细胞的氧化非常敏感，并且在体外与载脂蛋白A-I孵育后对氧化具有抵抗力。将apoA-I(但不是apoA-II或小鼠血清白蛋白)注射到小鼠体内，使其在3小时内抗氧化性。将apoA-I注入人体内，使其在6小时内抗氧化性。我们得出结论：1)动脉壁细胞氧化低密度脂蛋白需要播种包括HPODE和HPETE在内的分子；2)遗传易感于动脉粥样硬化的小鼠的低密度脂蛋白更容易被动脉壁细胞氧化；以及3)正常的高密度脂蛋白及其成分可以去除或抑制新分离的低密度脂蛋白中人类动脉壁细胞氧化所需的脂质的活性。
Apolipoprotein A-I (apoA-I) and an apoA-I peptide mimetic removed seeding molecules from human low density lipoprotein (LDL) and rendered the LDL resistant to oxidation by human artery wall cells. The apoA-I-associated seeding molecules included hydroperoxyoctadecadienoic acid (HPODE) and hydroperoxyeicosatetraenoic acid (HPETE). LDL from mice genetically susceptible to fatty streak lesion formation was highly susceptible to oxidation by artery wall cells and was rendered resistant to oxidation after incubation with apoA-I in vitro. Injection of apoA-I (but not apoA-II or murine serum albumin) into mice rendered their LDL resistant to oxidation within 3 h. Infusion of apoA-I into humans rendered their LDL resistant to oxidation within 6 h. We conclude that 1) oxidation of LDL by artery wall cells requires seeding molecules that include HPODE and HPETE; 2) LDL from mice genetically susceptible to atherogenesis is more readily oxidized by artery wall cells; and 3) normal HDL and its components can remove or inhibit the activity of lipids in freshly isolated LDL that are required for oxidation by human artery wall cells.