Beyond high-density lipoprotein cholesterol levels evaluating high-density lipoprotein function as influenced by...

Area of Science:

• Cardiovascular Research
• Lipid Metabolism
• Atherosclerosis Therapeutics

Background:

• Therapeutic strategies targeting high-density lipoprotein (HDL) cholesterol and reverse cholesterol transport are under development for atherosclerosis.
• Circulating HDL cholesterol levels alone are insufficient to measure the efficacy of these interventions.
• Assessing HDL function and identifying reliable surrogate markers are essential for evaluating HDL-targeted therapies.

Purpose of the Study:

• To highlight the need for reliable assays to evaluate the functional capacity of HDL in the context of atherosclerosis.
• To emphasize the importance of assessing macrophage cholesterol efflux and reverse cholesterol transport as key HDL functions.
• To underscore the necessity for developing robust and widely applicable assays for HDL functionality.

Main Methods:

• Review of current understanding of HDL's role in reverse cholesterol transport and atherosclerosis.
• Discussion of various dimensions of HDL functionality beyond cholesterol efflux, including effects on monocyte chemotaxis, endothelial inflammation, oxidation, nitric oxide production, and thrombosis.
• Identification of the need for in vivo methods to assess HDL's impact on reverse cholesterol transport.

Main Results:

• HDL cholesterol levels are inadequate predictors of therapeutic efficacy for atherosclerosis.
• Macrophage cholesterol efflux and reverse cholesterol transport are critical mechanisms of HDL's atheroprotective effects.
• Multiple facets of HDL functionality (e.g., anti-inflammatory, anti-oxidative) contribute to its protective role.

Conclusions:

• Reliable and reproducible assays for HDL function are critically needed to advance the field of HDL-targeted therapies.
• Such assays will enable effective assessment of the therapeutic potential of interventions aimed at modulating HDL.
• Moving forward requires the development and widespread adoption of functional HDL assays.