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High-density lipoproteins as therapeutic targets
Stephen J Nicholls1, Kerry-Anne Rye, Philip J Barter
1The Heart Research Institute, Sydney, Australia.
Current Opinion in Lipidology
|May 14, 2005
Summary
High-density lipoprotein (HDL) cholesterol concentration predicts cardiovascular disease risk. Recent findings show HDL’s protective role in inflammation and potential benefits of HDL-raising therapies, particularly cholesteryl ester transfer protein inhibitors.
Area of Science:
- Cardiovascular Research
- Lipid Metabolism
- Atherosclerosis
Background:
- High-density lipoprotein (HDL) cholesterol levels are inversely associated with cardiovascular disease risk.
- HDL particles possess antiatherogenic, antioxidant, anti-inflammatory, and antithrombotic properties.
- Cholesterol efflux from cells is a primary antiatherogenic function of HDL.
Purpose of the Study:
- To review recent findings on the protective role of HDL in acute inflammation.
- To discuss novel HDL-raising therapies, including cholesteryl ester transfer protein inhibitors.
- To reconcile conflicting research on HDL particle size and atheroprotection.
Main Methods:
- Review of recent scientific literature on HDL function and therapy.
- Analysis of studies investigating ATP-binding cassette transporter G1 (ABCG1) in cholesterol efflux.
- Evaluation of research on cholesteryl ester transfer protein (CETP) inhibitors.
Main Results:
- HDL demonstrates a significant protective role in acute inflammatory states.
- Novel CETP inhibitors show promising results as HDL-raising agents.
- ABCG1 facilitates cholesterol transport to large HDL particles, clarifying HDL's antiatherogenic role.
Conclusions:
- ABCG1-mediated cholesterol efflux to large HDL particles supports the atheroprotective effects of HDL.
- CETP inhibition, by increasing HDL size, may enhance cholesterol efflux and inhibit atherosclerosis development.