Montreal Heart Institute, Atherosclerosis Research Group.
Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
Curr Opin Lipidol. 2019 Apr;30(2):101-107. doi: 10.1097/MOL.0000000000000589.
The validity of HDL-cholesterol (HDL-C) elevation as a therapeutic target has been questioned, in comparison to enhancing HDL functionality. Cholesterol efflux capacity (CEC) is an in-vitro assay that measures the ability of an individual's HDL to promote cholesterol efflux from cholesterol donor cells such as macrophages. CEC of HDL is a predictor of cardiovascular risk independent of HDL-C levels. However, molecular determinants of CEC and the effects of diseases and therapeutic interventions on CEC have not been completely defined.
We review here recent findings on elevated HDL-C and disease risk, as well as determinants of CEC, from genetics and proteomics to pathophysiology and therapeutic interventions that contribute to our understanding of CEC as a biomarker of HDL functionality.
Elevated HDL-C levels are not always protective against cardiovascular disease and mortality. CEC is a heritable trait, and genetic polymorphisms in genes involved in HDL and triglycerides metabolism are associated with CEC. Multiple HDL proteins correlate positively with CEC levels and inversely with noncalcified plaque burden. Differences in CEC assays that make comparisons between studies difficult are also emphasized. CEC should be measured in clinical trials of lipid-modifying and anti-inflammatory therapies to determine whether increases are cardioprotective.
与增强 HDL 功能相比，高密度脂蛋白胆固醇（HDL-C）升高作为治疗靶点的有效性受到了质疑。胆固醇流出能力（CEC）是一种体外检测方法，用于测量个体 HDL 促进胆固醇从胆固醇供体细胞（如巨噬细胞）中流出的能力。HDL 的 CEC 是心血管风险的独立预测因子，与 HDL-C 水平无关。然而，CEC 的分子决定因素以及疾病和治疗干预对 CEC 的影响尚未完全确定。
本文综述了最近关于 HDL-C 升高与疾病风险的发现，以及 CEC 的决定因素，从遗传学和蛋白质组学到病理生理学和治疗干预，这些都有助于我们理解 CEC 作为 HDL 功能的生物标志物。
HDL-C 水平升高并不总是对心血管疾病和死亡率有保护作用。CEC 是一种可遗传的特征，与 HDL 和甘油三酯代谢相关基因的遗传多态性与 CEC 相关。多种 HDL 蛋白与 CEC 水平呈正相关，与非钙化斑块负担呈负相关。还强调了不同的 CEC 检测方法使得难以进行研究间的比较。在脂质调节和抗炎治疗的临床试验中应测量 CEC，以确定增加是否具有心脏保护作用。
