Rohatgi Anand
Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Prog Cardiovasc Dis. 2015 Jul-Aug;58(1):32-40. doi: 10.1016/j.pcad.2015.05.004. Epub 2015 May 9.
A low plasma level of high-density lipoprotein (HDL) cholesterol (HDL-C) is a major risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). However, several observations have highlighted the shortcomings of using cholesterol content as the sole reflection of HDL metabolism. In particular, several large randomized controlled trials of extended release niacin and cholesteryl-ester transfer protein (CETP) inhibitors on background statin therapy have failed to show improvement in ASCVD outcomes despite significant increases in HDL-C. Reverse cholesterol transport (RCT) is the principal HDL function that impacts macrophage foam cell formation and other functions such as endothelial activation of endothelial nitric oxide synthase, monocyte adhesion, and platelet aggregation. Cholesterol efflux from macrophages to plasma/serum reflects the first critical step of RCT and is considered a key anti-atherosclerotic function of HDL. Whether this function is operative in humans remains to be seen, but recent studies assessing cholesterol efflux in humans suggest that the cholesterol efflux capacity (CEC) of human plasma or serum is a potent marker of ASCVD risk. This review describes the methodology of measuring CEC ex vivo from human samples and the findings to date linking CEC to human disease. Studies to date confirm that CEC can be reliably measured using stored human blood samples as cholesterol acceptors and suggest that CEC may be a promising new biomarker for atherosclerotic and metabolic diseases. Further studies are needed to standardize measurements and clarify the role CEC may play in predicting risk of developing disease and response to therapies.
血浆中高密度脂蛋白（HDL）胆固醇（HDL-C）水平较低是动脉粥样硬化性心血管疾病（ASCVD）发生的主要危险因素。然而，一些观察结果突出了将胆固醇含量作为HDL代谢唯一反映指标的不足之处。特别是，几项关于缓释烟酸和胆固醇酯转运蛋白（CETP）抑制剂在他汀类药物背景治疗基础上进行的大型随机对照试验，尽管HDL-C显著升高，但并未显示出ASCVD结局得到改善。逆向胆固醇转运（RCT）是HDL的主要功能，它影响巨噬细胞泡沫细胞形成以及其他功能，如内皮型一氧化氮合酶的内皮激活、单核细胞黏附和血小板聚集。巨噬细胞向血浆/血清的胆固醇流出反映了RCT的第一个关键步骤，被认为是HDL的关键抗动脉粥样硬化功能。这种功能在人类中是否起作用还有待观察，但最近评估人类胆固醇流出的研究表明，人血浆或血清的胆固醇流出能力（CEC）是ASCVD风险的有力标志物。这篇综述描述了从人类样本中离体测量CEC的方法以及迄今为止将CEC与人类疾病联系起来的研究结果。迄今为止的研究证实，可以使用储存的人类血液样本作为胆固醇受体可靠地测量CEC，并表明CEC可能是动脉粥样硬化和代谢性疾病一个有前景的新生物标志物。需要进一步研究来规范测量方法，并阐明CEC在预测疾病发生风险和对治疗反应方面可能发挥的作用。
