State-of-the-Art Paper
Beyond High-Density Lipoprotein Cholesterol Levels: Evaluating High-Density Lipoprotein Function as Influenced by Novel Therapeutic Approaches

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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.

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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Dr. Rader is supported by grants from the National Heart, Lung, and Blood Institute (HL22633, HL70128) and is a recipient of the Doris Duke Charitable Foundation Distinguished Clinical Scientist Award. Dr. Rader has had research support from and consulted for Abbott Laboratories, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly and Co., Merck, Merck/Schering-Plough, Novartis, Pfizer, and Wyeth on topics related to high-density lipoprotein cholesterol. Dr. deGoma has received honoraria from Abbott Laboratories, AstraZeneca, and Merck/Schering-Plough for speaking on the management of dyslipidemia in clinical practice.