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在PCSK9相关的家族性高胆固醇血症中,用于识别HDL结构-功能关系的综合欧米学方法

Maryam Darabi¹, Marie Lhomme², Maharajah Ponnaiah³

¹Sorbonne Université, INSERM (Drs Darabi, Guillas, Frisdal, Poupel, Carrie,Bittar, Guerin, Le Goff, and Kontush), Institute of Cardiometabolism and Nutrition (ICAN), UMR_S1166, F-75013 Paris, France; LPS-BioSciences (Current affiliation of Dr Darabi), Université de Paris-Saclay, Orsay, France.

Journal of clinical lipidology

|August 7, 2023

概括

功能增益的PCSK9变体会损害高密度脂蛋白 (HDL) 的功能并改变其组成,从而导致心血管风险. 这项研究揭示了对HDL的新见解.

科学领域:

心血管生物学心血管生物学
脂质代谢脂质代谢是什么
蛋白质组学和葡萄糖组学

背景情况:

蛋白转化酶亚提利辛/素9型 (PCSK9) 在LDL受体活性之外的失脂症中起作用.
PCSK9对高密度脂蛋白 (HDL) 生理学的影响可能会影响心血管风险.

研究的目的:

评估PCSK9驱动的HDL生理学的改变.
调查这些改变对心血管风险概况的贡献.

主要方法:

从患有家族性高胆固醇血症 (FH) 的患者中分离出HDL,其中PCSK9获得功能 (FH-PCSK9),FH具有LDL-R变异 (已治疗和未治疗),以及正常脂质控制.
在HDL上进行了功能,蛋白质,脂质和糖质分析.
通过网络分析开发了HDL生物学的一种新的马赛克结构-功能模型.

主要成果:

患有FH-PCSK9的患者表现出多种HDL功能缺陷,包括减少抗氧化,抗瘤,抗血栓和抗炎活性.
在FH-PCSK9患者中,HDL细胞胆固醇流量能力保持不变.
观察到HDL蛋白质组合,脂质组合和糖质组合的明显变化,富含溶解脂,A2G2S2甘氨酸和阿波利波蛋白A-IV.

结论:

在FH-PCSK9患者中,抗原性HDL功能发生变化,伴随着特定的组成变化.
这项研究首次全面概述了PCSK9基因变异如何影响HDL结构-功能关系.

关键词:

计算生物学是一种计算生物学.家庭性高胆固醇血症是什么?获得功能突变的突变.高密度脂蛋白是一种高密度脂蛋白.低密度脂蛋白受体的受体是低密度脂蛋白受体.蛋白转化酶子素素9型 9型

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