HDL, ABC transporters, and cholesterol efflux: implications for the treatment of atherosclerosis

Area of Science:

• Cardiovascular Science
• Molecular Biology
• Pharmacology

Background:

• High-density lipoprotein (HDL) is a potential therapeutic target for atherosclerotic vascular disease.
• The cholesteryl ester transfer protein (CETP) inhibitor torcetrapib failed to demonstrate efficacy, raising questions about HDL-raising strategies.
• Torcetrapib's failure may be due to off-target toxicity, not inherent inefficacy of HDL elevation.

Purpose of the Study:

• To re-evaluate the therapeutic potential of increasing HDL levels for treating atherosclerosis.
• To highlight the role of ATP-binding cassette (ABC) transporters in HDL's atheroprotective functions.

Main Methods:

• Review of recent analyses and studies on HDL function and atherosclerosis.
• Focus on the roles of ABCA1 and ABCG1 transporters in macrophage biology and disease progression.

Main Results:

• HDL is functional and can promote atherosclerosis regression.
• ATP-binding cassette transporters ABCA1 and ABCG1 are crucial for reducing macrophage foam cell formation.
• These transporters also play a key role in mitigating inflammation associated with atherosclerosis.

Conclusions:

• Despite past setbacks, HDL-targeted therapies remain a promising avenue for atherosclerosis treatment.
• Strategies focusing on enhancing the function of ABCA1 and ABCG1 may be effective.
• Further research into various HDL-raising approaches is warranted for developing successful atherosclerosis treatments.