Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions
Lipoprotein-associated phospholipase A2, platelet-activating factor acetylhydrolase, is expressed by macrophages in human and rabbit atherosclerotic lesions
复制标题
DOI：
10.1161/01.atv.19.12.2909
复制
发表时间：
1999-12-01
影响因子：
8.7
通讯作者：
Ylä-Herttuala, S
中科院分区：
文献类型：
--
作者：
Häkkinen, T;Luoma, JS;Ylä-Herttuala, S
我们研究了人和兔动脉粥样硬化病变中脂蛋白相关磷脂酶A（2）（Lp-PLA（2））的表达，Lp-PLA（2）是一种能够水解血小板活化因子（PAF）、PAF样磷脂和极性修饰磷脂酰胆碱的酶。低密度脂蛋白的氧化修饰在动脉粥样硬化形成中起重要作用，产生具有生物活性的具有极性脂肪酸链的PAF样修饰磷脂衍生物。已知PAF具有强的促炎活性，并且通过其水解而失活。另一方面，氧化低密度脂蛋白由于Lp-PLA（2）活性而释放的溶血磷脂酰胆碱和氧化脂肪酸被认为与动脉粥样硬化的进展有关。应用原位杂交和免疫细胞化学相结合的方法，检测了人和兔动脉粥样硬化病变巨噬细胞内脂蛋白-磷脂酰乳酸（2）（Lp-PLA（2））mRNA和蛋白的表达。逆转录-聚合酶链反应分析表明，人动脉粥样硬化病变中Lp-PLA（2）mRNA的表达增加。此外，在Watanabe遗传性高脂血症兔的动脉粥样硬化动脉瘤中检测到的Lp-PLA（2）活性比对照兔的正常动脉瘤高约6倍。结论是：（1）人和兔动脉粥样硬化病变中的巨噬细胞表达Lp-PLA（2），其可以切割病变区域中存在的任何氧化修饰的磷脂酰胆碱，（2）Lp-PLA（2）活性的调节可以导致血管壁中的抗动脉粥样硬化作用。
We studied the expression of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an enzyme capable of hydrolyzing platelet-activating factor (PAF), PAF-like phospholipids, and polar-modified phosphatidylcholines, in human and rabbit atherosclerotic lesions. Oxidative modification of low-density lipoprotein, which plays an important role in atherogenesis, generates biologically active PAF-like modified phospholipid derivatives with polar fatty acid chains. PAF is known to have a potent proinflammatory activity and is inactivated by its hydrolysis. On the other hand, lysophosphatidylcholine and oxidized fatty acids released from oxidized low-density lipoprotein as a result of Lp-PLA(2) activity are thought to be involved in the progression of atherosclerosis. Using combined in situ hybridization and immunocytochemistry, we detected Lp-PLA(2) mRNA and protein in macrophages in both human and rabbit atherosclerotic lesions. Reverse transcriptase-polymerase chain reaction analysis indicated an increased expression of Lp-PLA(2) mRNA in human atherosclerotic lesions. In addition, approximate to 6-fold higher Lp-PLA(2) activity was detected in atherosclerotic aortas of Watanabe heritable hyperlipidemic rabbits compared with normal aortas from control rabbits. It is concluded that (1) macrophages in both human and rabbit atherosclerotic lesions express Lp-PLA(2), which could cleave any oxidatively modified phosphatidylcholine present in the lesion area, and (2) modulation of Lp-PLA(2) activity could lead to antiatherogenic effects in the vessel wall.