HDL and reverse cholesterol transport in humans and animals: Lessons from pre-clinical models and clinical studies

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• High-density lipoprotein (HDL) is recognized for its antiatherogenic function via reverse cholesterol transport (RCT).
• Animal models and human studies have elucidated HDL's mechanisms in cholesterol efflux and hepatic uptake.
• HDL composition and lipid transporters significantly influence RCT processes.

Purpose of the Study:

• To review the critical role of HDL in reverse cholesterol transport (RCT).
• To discuss methodologies used to assess HDL's function in RCT.
• To evaluate the clinical utility of cholesterol efflux capacity (CEC) as a biomarker.

Main Methods:

• Analysis of data from animal models, including transgenic and intervention studies.
• Review of human cohort studies investigating HDL function and cardiovascular risk.
• Examination of in vitro assays like cholesterol efflux capacity (CEC) for measuring RCT.

Main Results:

• HDL facilitates cholesterol removal from macrophages and transport to the liver, a key antiatherogenic mechanism.
• Cholesterol efflux capacity (CEC) has shown associations with cardiovascular risk in some human populations.
• Conflicting data on CEC validity as a biomarker necessitates further investigation.

Conclusions:

• HDL-mediated RCT is a crucial protective mechanism against atherosclerosis.
• While CEC shows promise, its reliability as a standalone biomarker requires further validation.
• Continued research using diverse methodologies is essential to fully understand HDL's role in cardiovascular health.