Playford Martin P, Neufeld Edward B, Zubirán Rafael, Remaley Alan T
Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, NIH, Bethesda, MD, United States.
Lipoprotein Metabolism Laboratory, National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, MD, United States.
Front Cardiovasc Med. 2025 Jul 10;12:1608384. doi: 10.3389/fcvm.2025.1608384. eCollection 2025.
The removal of excess cholesterol from the body by High-density lipoprotein (HDL) in a process termed reverse cholesterol transport (RCT) has long been proposed to play a critical role in reduction of the lipid burden in arterial wall atherosclerotic lesions. While HDL-cholesterol levels are associated with decreased cardiovascular risk and considered to be "good-cholesterol", clinical studies using HDL-raising therapies to potentially enhance RCT have consistently produced disappointing results. In this mini review we evaluate the effects of human disease on RCT along with the changes in this process upon various therapeutic interventions. Despite the importance of assay standardization, the major method for monitoring RCT has relied upon the cholesterol efflux capacity (CEC) assay, a highly-difficult and tedious cell culture assay, which is low-throughput and only suitable for research studies. Hence, we also briefly review several new methods to measure RCT both and along with new cell-free alternative RCT assays, which have the potential to be developed into routine automated diagnostic assay. The benefits of HDL may yet be revealed by the use of these new high-throughput RCT assays perhaps as a screening tool for novel RCT boosting agents or as new biomarkers for cardiovascular disease risk.
长期以来,人们一直认为高密度脂蛋白(HDL)通过逆向胆固醇转运(RCT)过程从体内清除多余胆固醇,这在减轻动脉壁动脉粥样硬化病变中的脂质负担方面起着关键作用。虽然HDL胆固醇水平与心血管风险降低相关,并被认为是“好胆固醇”,但使用升高HDL疗法以潜在增强RCT的临床研究一直产生令人失望的结果。在本综述中,我们评估了人类疾病对RCT的影响以及各种治疗干预对此过程的改变。尽管检测标准化很重要,但监测RCT的主要方法一直依赖于胆固醇流出能力(CEC)检测,这是一种高度困难且繁琐的细胞培养检测方法,通量低且仅适用于研究。因此,我们还简要回顾了几种测量RCT的新方法以及新的无细胞替代RCT检测方法,这些方法有可能发展成为常规自动化诊断检测。使用这些新的高通量RCT检测方法,HDL的益处可能会被揭示,也许可作为新型RCT增强剂的筛选工具或作为心血管疾病风险的新生物标志物。