STATE-OF-THE-ART PAPER
Beyond High-Density Lipoprotein Cholesterol LevelsEvaluating High-Density Lipoprotein Function as Influenced by Novel Therapeutic Approaches
Emil M. deGoma, MD*,*,
Rolando L. deGoma, MD and
Daniel J. Rader, MD ,*
* Department of Cardiology, Stanford University Hospital, Stanford, California
New Jersey Preventive Cardiology, Trenton, New Jersey
Institute for Translational Medicine and Therapeutics, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania.
Manuscript received September 17, 2007;
revised manuscript received February 19, 2008,
accepted March 4, 2008.
* Reprint requests and correspondence: Dr. Emil M. deGoma, Stanford University Hospital, Falk Cardiovascular Research Center, 300 Pasteur Drive, Stanford, California 94305. (Email: edegoma{at}stanford.edu). * Dr. Daniel J. Rader, Cardiovascular Institute and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, 654 BRBII/III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104. (Email: rader{at}mail.med.upenn.edu).
A number of therapeutic strategies targeting high-density lipoprotein (HDL) cholesterol and reverse cholesterol transport are being developed to halt the progression of atherosclerosis or even induce regression. However, circulating HDL cholesterol levels alone represent an inadequate measure of therapeutic efficacy. Evaluation of the potential effects of HDL-targeted interventions on atherosclerosis requires reliable assays of HDL function and surrogate markers of efficacy. Promotion of macrophage cholesterol efflux and reverse cholesterol transport is thought to be one of the most important mechanisms by which HDL protects against atherosclerosis, and methods to assess this pathway in vivo are being developed. Indexes of monocyte chemotaxis, endothelial inflammation, oxidation, nitric oxide production, and thrombosis reveal other dimensions of HDL functionality. Robust, reproducible assays that can be performed widely are needed to move this field forward and permit effective assessment of the therapeutic potential of HDL-targeted therapies.
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Abbreviations and Acronyms
| | CAD = coronary artery disease | | CETP = cholesteryl ester transfer protein | | FMD = flow-mediated dilation | | HDL = high-density lipoprotein | | HUVEC = human umbilical endothelial cell | | ICAM = intercellular adhesion molecule | | LDL = low-density lipoprotein | | NO = nitric oxide | | NOS = nitric oxide synthase | | RCT = reverse cholesterol transport | | TNF = tumor necrosis factor | | VCAM = vascular cell adhesion molecule |
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