Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.
Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis.
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DOI：
10.1056/nejmoa1001689
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发表时间：
2011-01-13
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影响因子：
--
通讯作者：
Rader DJ
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作者：
Khera AV;Cuchel M;de la Llera-Moya M;Rodrigues A;Burke MF;Jafri K;French BC;Phillips JA;Mucksavage ML;Wilensky RL;Mohler ER;Rothblat GH;Rader DJ
高密度脂蛋白(高密度脂蛋白)可能通过促进巨噬细胞的胆固醇反向运输来提供心血管保护。我们假设，高密度脂蛋白从巨噬细胞接受胆固醇的能力将作为动脉粥样硬化负担的预测因子。我们测量了203名接受颈动脉内中膜厚度评估的健康志愿者、442名经血管造影证实的冠状动脉疾病患者和351名未经血管造影证实的冠心病患者的胆固醇流出能力。我们使用一个有效的体外系统来量化外排能力，该系统包括用研究参与者的载脂蛋白B耗尽的血清孵育巨噬细胞。高密度脂蛋白胆固醇和载脂蛋白A-I的水平是胆固醇外流能力的重要决定因素，但对观察到的变化的解释不到40%。在调整高密度脂蛋白胆固醇水平前后，流出能力和颈动脉内膜-中层厚度之间存在负相关关系。此外，外排能力是冠状动脉疾病状态的一个强大的反向预测因子(每1-SD外排能力增加调整后的冠心病优势比为0.7；95%可信区间[CI]为0.59至0.83；P<；0.001)。在对高密度脂蛋白胆固醇水平(每1-SD增加的优势比，0.75；95%CI，0.63至0.9；P=0.002)或载脂蛋白A-I水平(每1-SD增加的优势比，0.74；95%CI，0.61至0.89；P=0.002)进行额外调整后，这种关系有所减弱，但仍显著。其他研究表明，服用吡格列酮治疗的代谢综合征和低高密度脂蛋白胆固醇水平的患者的外排能力增强，但使用他汀类药物治疗的高胆固醇血症患者的外排能力没有改善。巨噬细胞的胆固醇流出能力是衡量高密度脂蛋白功能的一个指标，它与颈动脉内中膜厚度和冠状动脉造影术中冠状动脉疾病的可能性呈强烈的负相关，与高密度脂蛋白水平无关。(由国家心肺血液研究所等资助。)
High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden. We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima–media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B–depleted serum from the study participants. The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima–media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P = 0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P = 0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins. Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima–media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.)