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Effect of high-density lipoproteins on the expression of adhesion molecules in endothelial cells
Philip J Barter1, Paul W Baker, Kerry-Anne Rye
1Lipid Research Laboratory, Hanson Institute for Medical Research, Adelaide, Australia. philip.barter@adelaide.edu.au
Insights
High-density lipoproteins (HDLs) may protect against atherosclerosis by removing cholesterol from macrophages and inhibiting vascular cell adhesion molecule expression in endothelial cells. Further research is needed to clarify the exact mechanisms and in vivo contributions of these effects.
Area of Science:
- Cardiovascular Science
- Lipid Metabolism
- Atherosclerosis Research
Background:
- High-density lipoproteins (HDLs) are known for their role in reverse cholesterol transport.
- HDLs are increasingly recognized for potential anti-atherogenic properties beyond cholesterol efflux.
- Early events in atherosclerosis involve endothelial cell activation and adhesion molecule expression.
Purpose of the Study:
- To explore the mechanisms by which HDLs protect against atherosclerosis.
- To investigate the role of HDLs in inhibiting vascular cell adhesion molecule expression.
- To understand the influence of HDL composition on its inhibitory activity.
Main Methods:
- In vitro studies using native and reconstituted HDLs.
- In vivo studies in animal models (mice and pigs).
- Analysis of phospholipid composition's effect on HDL activity.
Main Results:
- HDLs promote cholesterol efflux from macrophages.
- HDLs inhibit vascular cell adhesion molecule expression in activated endothelial cells in vitro.
- Inhibition of adhesion molecule expression by HDLs was observed in some in vivo studies but not consistently.
Conclusions:
- HDLs possess multiple potential mechanisms for protecting against atherosclerosis.
- The inhibition of endothelial adhesion molecule expression is a potential anti-atherogenic effect of HDLs.
- The precise mechanism and in vivo significance of HDL's effect on adhesion molecules require further investigation.
Abstract:
There are several potential mechanisms by which HDLs protect against atherosclerosis. One relates to the ability of HDLs to promote the efflux of cholesterol from macrophages. Another is the ability of HDLs to inhibit one of the earliest events in the development of atherosclerosis, namely the expression of vascular cell adhesion molecules in activated endothelial cells. This property has been reported in vitro in studies with both native and reconstituted HDLs. The inhibitory activity of reconstituted HDLs is influenced by the phospholipid composition of the particles. An inhibition of endothelial cell adhesion molecule expression has also been observed in some (but not all) studies conducted in vivo in mice and pigs. The mechanism of this potentially anti-atherogenic effect of HDLs remains uncertain, as does its contribution to the cardioprotective effects of HDLs in vivo.