Forte Trudy M, Subbanagounder Ganesamoorthy, Berliner Judith A, Blanche Patricia J, Clermont Anne O, Jia Zhen, Oda Michael N, Krauss Ronald M, Bielicki John K
Life Sciences Division MS 1-222, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
J Lipid Res. 2002 Mar;43(3):477-85.
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.
我们研究了在8周龄的动脉粥样硬化易感载脂蛋白E（apoE）基因敲除（-/-）和低密度脂蛋白受体（LDLr）基因敲除（-/-）小鼠中，假定的抗动脉粥样硬化酶卵磷脂胆固醇酰基转移酶（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，以及生物活性氧化磷脂的血浆浓度是否在血浆中积累。与正常饮食的对照组相比，apoE（-/-）小鼠的LCAT活性降低了28%，溶血磷脂酰胆碱以及生物活性氧化磷脂（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）水平升高。氧化磷脂升高和LCAT活性降低可能部分导致了这些正常饮食小鼠的自发性病变。西式饮食进一步降低了LCAT活性（降至对照组的50%），PON活性降低了38%。LDLr（-/-）小鼠在正常饮食时LCAT活性正常，氧化磷脂积累很少。在西式饮食下，LDLr（-/-）小鼠的LCAT活性降低（降至21%），但PON活性没有变化。所有基因型在西式饮食下PAF-AH活性均降低。在西式饮食下，apoE（-/-）和LDLr（-/-）小鼠（而非对照组）的血浆生物活性氧化磷脂升高。我们得出结论，LCAT活性受损和氧化磷脂积累是这些模型早期动脉粥样硬化表型的一部分。
