Therapeutic Targeting of HDL and Reverse Cholesterol Transport

Author(s): D. Sviridov .

Journal Name: Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents

Volume 5 , Issue 4 , 2005

Abstract:

Reverse cholesterol transport (RCT) is one pathway for removing excessive cholesterol from extrahepatic cells and tissues and eventual transport to the liver for excretion thus reducing the accumulation of cholesterol in arteries. Activity of RCT is believed to be affected at least partially by the high density lipoprotein (HDL) concentration in the blood, since HDL is the major carrier of cellular cholesterol through RCT. This presumption lead to an assertion that raising HDL-C levels alone would improve RCT and provide enhanced protection against development of atherosclerosis. However, studies on RCT show that the concentration of HDL required for maximum recruitment of cellular cholesterol is far below the concentration of HDL in plasma. A more likely explanation is that the rate of RCT and the HDL concentration, which is partially determined by RCT, protect against atherosclerosis independently of each other. RCT may result in formation of dysfunctional HDL and a high level of HDL-C is not always synonymous with an efficient RCT. RCT consists of three major stages: cholesterol efflux, transport of cholesterol through the plasma compartment and uptake and excretion of cholesterol by liver. Each stage is a muti-step pathway or a combination of parallel pathways. The contribution and overall efficiency of these pathways often depends on specific metabolic circumstances. Finding the determinants of RCT would be valuable for choosing targets and evaluating the efficiency of possible therapy aimed at boosting RCT, raising HDL and enhancing protection against atherosclerosis.

Keywords: reverse cholesterol transport, high density lipoprotein, atherosclerosis, lipoproteins, coronary heart disease

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Article Details

VOLUME: 5
ISSUE: 4
Year: 2005
Page: [299 - 307]
Pages: 9
DOI: 10.2174/1568013054637803
Price: $58