Platelet-activating factor acetylhydrolase is mainly associated with electronegative low-density lipoprotein subfraction

Platelet-activating factor acetylhydrolase is mainly associated with electronegative low-density lipoprotein subfraction
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DOI:
10.1161/01.cir.0000072791.40232.8f
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发表时间:
2003-07-08
期刊:
影响因子:
37.8
通讯作者:
Ordóñez-Llanos, J
Ordóñez-Llanos, J
中科院分区:
医学1区
文献类型:
--
作者:
Benítez, S;Sánchez-Quesada, JL;Ordóñez-Llanos, J

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背景-电阴性 LDL [LDL(-)] 是血浆中 LDL 的修饰亚组分,可诱导培养的内皮细胞释放白细胞介素 8 和单核细胞趋化蛋白 1。 方法和结果 - 我们证明血小板活化因子乙酰水解酶 (PAF-AH) 主要与 LDL(-) 相关。在正常血脂和家族性高胆固醇血症受试者中,LDL(-) 的 PAF-AH 活性比非电阴性 LDL 亚组分 [LDL(+)] 高 5 倍。 SDS-PAGE后的蛋白质印迹分析证实了这些结果,因为对应于PAF-AH的单个44 kDa条带出现在LDL(-)中,但不在LDL(+)中。非变性聚丙烯酰胺梯度凝胶电泳证明,无论 LDL 大小如何,PAF-AH 均与 LDL(-) 结合。根据上述发现,与 LDL(+) 相比,LDL(-) 中 PAF-AH 的裂解产物非酯化脂肪酸增加。结论 - LDL(-) 中观察到的高 PAF-AH 活性可能与这些脂蛋白对培养的内皮细胞的促炎活性有关。
Background-Electronegative LDL [LDL(-)], a modified subfraction of LDL present in plasma, induces the release of interleukin-8 and monocyte chemotactic protein-1 from cultured endothelial cells.Methods and Results - We demonstrate that platelet-activating factor acetylhydrolase (PAF-AH) is mainly associated with LDL(-). LDL(-) had 5-fold higher PAF-AH activity than the nonelectronegative LDL subfraction [LDL(+)] in both normolipemic and familial hypercholesterolemic subjects. Western blot analysis after SDS-PAGE confirmed these results, because a single band of 44 kDa corresponding to PAF-AH appeared in LDL(-) but not in LDL(+). Nondenaturing polyacrylamide gradient gel electrophoresis demonstrated that PAF-AH was bound to LDL(-) regardless of LDL size. In accordance with the above findings, nonesterified fatty acids, a cleavage product of PAF-AH, were increased in LDL(-) compared with LDL(+).Conclusions - The high PAF-AH activity observed in LDL(-) could be related to the proinflammatory activity of these lipoproteins toward cultured endothelial cells.