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High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport
A von Eckardstein1, J R Nofer, G Assmann
1Institut für Klinische Chemie und Laboratoriumsmedizin, Zentrallaboratorium, Westfälische Wilhelms-Universität Münster, Germany. vonecka@uni-muenster.de
Insights
High density lipoprotein (HDL) cholesterol is linked to heart disease. Its subclasses, not just levels, are key to cholesterol removal and reducing atherosclerosis risk.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
Background:
- High density lipoprotein (HDL) cholesterol is a significant risk factor for coronary heart disease.
- HDL possesses antiatherogenic properties, notably mediating cholesterol efflux and reverse cholesterol transport (RCT) from arterial cells to the liver.
- Enhancing cholesterol efflux and RCT is a primary therapeutic target for antiatherosclerotic drug development.
Purpose of the Study:
- To investigate the determinants of reverse cholesterol transport (RCT) efficacy and its relationship with atherosclerosis risk.
- To clarify the role of HDL subclasses and metabolism kinetics in RCT, beyond total HDL cholesterol levels.
Main Methods:
- In vitro experiments
- Genetic family and population studies
- Investigation of transgenic animal models
Main Results:
- HDL cholesterol plasma levels do not always correlate with RCT efficacy or antiatherogenicity.
- Concentration of specific HDL subclasses is crucial for effective RCT.
- Cellular lipid mobilization for efflux and HDL metabolism kinetics are critical factors in RCT.
Conclusions:
- HDL subclasses, cellular lipid efflux, and HDL metabolism kinetics are more important determinants of RCT efficacy than total HDL cholesterol levels.
- These factors significantly influence atherosclerosis risk.
Abstract:
High density lipoprotein (HDL) cholesterol is an important risk factor for coronary heart disease, and HDL exerts various potentially antiatherogenic properties, including the mediation of reverse transport of cholesterol from cells of the arterial wall to the liver and steroidogenic organs. Enhancement of cholesterol efflux and of reverse cholesterol transport (RCT) is considered an important target for antiatherosclerotic drug therapy. Levels and composition of HDL subclasses in plasma are regulated by many factors, including apolipoproteins, lipolytic enzymes, lipid transfer proteins, receptors, and cellular transporters. In vitro experiments as well as genetic family and population studies and investigation of transgenic animal models have revealed that HDL cholesterol plasma levels do not necessarily reflect the efficacy and antiatherogenicity of RCT. Instead, the concentration of HDL subclasses, the mobilization of cellular lipids for efflux, and the kinetics of HDL metabolism are important determinants of RCT and the risk of atherosclerosis.