Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood
Featured Article: Alterations of lecithin cholesterol acyltransferase activity and apolipoprotein A-I functionality in human sickle blood
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DOI：
10.1177/1535370216657447
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发表时间：
2016-11-01
影响因子：
3.2
通讯作者：
Kuypers, Frans A.
中科院分区：
文献类型：
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作者：
Soupene, Eric;Borja, Mark S.;Kuypers, Frans A.
在镰状细胞病 (SCD) 中，胆固醇代谢出现功能障碍，SCD 患者亚群血浆胆固醇含量异常即可证明这一点。镰刀血浆中高密度脂蛋白 (HDL) 结合卵磷脂胆固醇酰基转移酶 (LCAT) 的比活性显着低于正常值，该酶催化胆固醇酯化并生成溶血 PC (LPC)。镰刀血浆中存在抑制量的 LPC，而对于去除 LPC 至关重要的红细胞 (RBC) 溶血磷脂酰胆碱酰基转移酶 (LPCAT) 表现出广泛的活性。与对照相比，镰状细胞血浆中 HDL-载脂蛋白 A-I 交换减少证明，镰状细胞 HDL 的功能似乎发生了改变。在镰状细胞血浆中检测到包括 ApoA-I 在内的氧化蛋白水平升高。镰状血浆与洗涤的红细胞的体外孵育影响了 ApoA-I 交换，支持红细胞血液区室可以影响血浆中胆固醇代谢的观点。在镰状细胞病患者的急性血管闭塞发作期间，HDL 功能似乎有所下降，并且与分泌性 PLA(2)（炎症增加的标志物）的增加有关。辛伐他汀治疗改善 HDL 的抗炎功能并没有改善镰状细胞病患者的 HDL-ApoA-I 交换。因此，镰状血中炎症和高氧化环境的累积效应导致胆固醇酯化和高密度脂蛋白功能降低，这与 SCD 中的低胆固醇血症有关。
In sickle cell disease (SCD) cholesterol metabolism appears dysfunctional as evidenced by abnormal plasma cholesterol content in a subpopulation of SCD patients. Specific activity of the high density lipoprotein (HDL)-bound lecithin cholesterol acyltransferase (LCAT) enzyme, which catalyzes esterification of cholesterol, and generates lysoPC (LPC) was significantly lower in sickle plasma compared to normal. Inhibitory amounts of LPC were present in sickle plasma, and the red blood cell (RBC) lysophosphatidylcholine acyltransferase (LPCAT), essential for the removal of LPC, displayed a broad range of activity. The functionality of sickle HDL appeared to be altered as evidenced by a decreased HDL-Apolipoprotein A-I exchange in sickle plasma as compared to control. Increased levels of oxidized proteins including ApoA-I were detected in sickle plasma. Invitro incubation of sickle plasma with washed erythrocytes affected the ApoA-I-exchange supporting the view that the RBC blood compartment can affect cholesterol metabolism in plasma. HDL functionality appeared to decrease during acute vaso-occlusive episodes in sickle patients and was associated with an increase of secretory PLA(2), a marker for increased inflammation. Simvastatin treatment to improve the anti-inflammatory function of HDL did not ameliorate HDL-ApoA-I exchange in sickle patients. Thus, the cumulative effect of an inflammatory and highly oxidative environment in sickle blood contributes to a decrease in cholesterol esterification and HDL function, related to hypocholesterolemia in SCD.