Current Atherosclerosis Reports

, Volume 12, Issue 1, pp 73–81

Future Therapeutic Directions in Reverse Cholesterol Transport



Despite a robust inverse association between high-density lipoprotein (HDL) cholesterol levels and atherosclerotic cardiovascular disease, the development of new therapies based on pharmacologic enhancement of HDL metabolism has proven challenging. Emerging evidence suggests that static measurement of HDL levels has inherent limitations as a surrogate for overall HDL functionality, particularly with regard to the rate of flux through the macrophage reverse cholesterol transport (RCT) pathway. Recent research has provided important insight into the molecular underpinnings of RCT, the process by which excess cellular cholesterol is effluxed from peripheral tissues and returned to the liver for ultimate intestinal excretion. This review discusses the critical importance and current strategies for quantifying RCT flux. It also highlights therapeutic strategies for augmenting macrophage RCT via three conceptual approaches: 1) improved efflux of cellular cholesterol via targeting the macrophage; 2) enhanced cholesterol efflux acceptor functionality of circulating HDL; and 3) increased hepatic uptake and biliary/intestinal excretion.


Reverse cholesterol transport High-density lipoprotein Lipid metabolism 

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Institute for Translational Medicine and Therapeutics and Cardiovascular InstituteUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.University of Pennsylvania School of Medicine654 BRBII/IIIPhiladelphiaUSA

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