MINI REVIEW article
Front. Cardiovasc. Med.
Sec. Lipids in Cardiovascular Disease
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1608384
This article is part of the Research TopicEvidence of Atherogenic Lipoproteins: what we gain from in vitro and in vivo researchView all 13 articles
Reverse Cholesterol Transport: Current assay methods, alterations with disease and response to therapeutic intervention
Provisionally accepted
- National Heart, Lung, and Blood Institute (NIH), Bethesda, United States
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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 in vitro and in vivo, 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.
Keywords: Cholesterol, ABCA1, ApoA1, Inflammation, reverse cholesterol transport (RCT)
Received: 08 Apr 2025; Accepted: 18 Jun 2025.
Copyright: © 2025 Playford, Neufeld, Zubiran and Remaley. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Martin Playford, National Heart, Lung, and Blood Institute (NIH), Bethesda, United States
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