Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice.
Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice.
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发表时间：
2002-03
影响因子：
6.5
通讯作者：
T. Forte;G. Subbanagounder;J. Berliner;P. Blanche;A. Clermont;Z. Jia;M. Oda;R. Krauss;J. Bielicki
中科院分区：
文献类型：
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作者：
T. Forte;G. Subbanagounder;J. Berliner;P. Blanche;A. Clermont;Z. Jia;M. Oda;R. Krauss;J. Bielicki
我们检测了8周龄动脉粥样硬化易感载脂蛋白E（apoE）（-/-）和LDL受体（LDLr）（-/-）小鼠中假定的抗动脉粥样硬化酶LCAT、对氧磷酶（PON）和血小板活化因子乙酰水解酶（PAF-AH）是否受损，以及血浆中生物活性氧化磷脂的血浆浓度是否在血浆中积累。与饲料对照组相比，ApoE（-/-）小鼠的LCAT活性降低（28%），溶血磷脂酰胆碱和生物活性氧化磷脂（1-棕榈酰-2-氧代戊酰-sn-甘油-3-磷酸胆碱和1-棕榈酰-2-戊二酰-sn-甘油-3-磷酸胆碱）升高。升高的氧化磷脂和降低的LCAT活性可能部分导致这些喂食普通饲料的小鼠中的自发性病变。西方饮食进一步降低LCAT活性（对照组的50%），PON活性降低38%。LDLr（-/-）小鼠在普通饲料中显示出正常的LCAT活性，氧化磷脂几乎没有蓄积。在西方饮食中，LDLr（-/-）小鼠的LCAT活性降低（21%），但PON活性没有变化。所有基因型的PAF-AH活性降低西方饮食。ApoE（-/-）和LDLr（-/-）小鼠（而非对照组）在西方饮食中血浆生物活性氧化磷脂升高。我们的结论是LCAT活性的损害和氧化磷脂的积累是这些模型中早期致动脉粥样硬化表型的一部分。
We examined whether the putative anti-atherogenic enzymes LCAT, paraoxonase (PON), and platelet-activating factor acetylhydrolase (PAF-AH) are impaired in 8 week old atherosclerosis susceptible apolipoprotein E (apoE)(-/-) and LDL receptor (LDLr)(-/-) mice and whether plasma concentrations of bioactive oxidized phospholipids accumulate in plasma. ApoE(-/-) mice had reduced (28%) LCAT activity and elevated lysophosphatidylcholine and bioactive oxidized phospholipids (1-palmitoyl-2-oxovaleryl-sn-glycero-3-phosphocholine and 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine) compared with controls on the chow diet. Elevated oxidized phospholipids and reduced LCAT activity may, in part, contribute to spontaneous lesions in these mice on a chow diet. A Western diet decreased LCAT activity further (50% of controls) and PON activity was decreased 38%. The LDLr(-/-) mice showed normal LCAT activity on chow diet and little accumulation of oxidized phospholipids. On a Western diet, LDLr(-/-) mice had reduced LCAT activity (21%), but no change in PON activity. All genotypes had reduced PAF-AH activity on the Western diet. ApoE(-/-) and LDLr(-/-) mice, but not controls, had elevated plasma bioactive oxidized phospholipids on the Western diet. We conclude that impairment of LCAT activity and accumulation of oxidized phospholipids are part of an early atherogenic phenotype in these models.