Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by novel therapeutic approaches |
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Authors: | deGoma Emil M deGoma Rolando L Rader Daniel J |
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Affiliation: | Department of Cardiology, Stanford University Hospital, Stanford, California 94305, USA. edegoma@stanford.edu |
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Abstract: | 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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Keywords: | 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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