JCL roundtable: High-density lipoprotein function and reverse cholesterol transport

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• High-density lipoproteins (HDL) have been historically linked to protection against atherosclerotic cardiovascular disease.
• Recent studies challenge this association, with some showing increased risk at very high HDL cholesterol levels.
• Clinical trials targeting HDL have failed to confirm its protective role.

Purpose of the Study:

• To discuss and elucidate the complex functions of HDL particles.
• To re-evaluate the mechanisms underlying HDL's role in atherosclerosis.
• To explore emerging concepts in HDL functionality and its clinical implications.

Main Methods:

• Roundtable discussion among 3 expert investigators in the HDL field.
• Review of epidemiological studies and randomized clinical trials.
• Discussion of functional bioassays, including cholesterol efflux capacity.
• Consideration of apolipoprotein composition (ApoA-I, ApoE, ApoC-III) and particle modifications.

Main Results:

• Agreement that reverse cholesterol transport is a primary hypothesis for HDL's anti-atherogenic function.
• Cholesterol efflux capacity assays are emerging as accurate surrogates for reverse cholesterol transport.
• Subpopulations of HDL containing ApoE and ApoC-III may play significant roles.
• Anti- and pro-inflammatory functions, along with oxidative modifications of HDL, are gaining attention.

Conclusions:

• The precise mechanisms of HDL's protective role in atherosclerosis remain unclear.
• Functional assays of HDL are crucial for understanding its true impact on cardiovascular health.
• Future research should investigate diverse HDL functions beyond cholesterol transport.