Reverse cholesterol transport: current assay methods, alterations with disease and response to therapeutic...

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Biomarker Discovery

Background:

• High-density lipoprotein (HDL) plays a key role in reverse cholesterol transport (RCT), removing excess cholesterol from arteries.
• Despite association with reduced cardiovascular risk, HDL-raising therapies have yielded disappointing clinical results.
• Human diseases and therapeutic interventions significantly impact RCT processes.

Purpose of the Study:

• To evaluate the impact of human diseases and therapeutic interventions on RCT.
• To review current and emerging methods for measuring RCT, addressing limitations of existing assays.
• To explore the potential of new assays for screening RCT-boosting agents and identifying cardiovascular disease biomarkers.

Main Methods:

• Review of existing literature on RCT, human diseases, and therapeutic interventions.
• Evaluation of the cholesterol efflux capacity (CEC) assay and its limitations.
• Exploration of novel in vitro and in vivo methods, including cell-free assays for RCT measurement.

Main Results:

• Existing HDL-raising therapies have shown limited success in clinical studies.
• The cholesterol efflux capacity (CEC) assay is a difficult, low-throughput method unsuitable for routine diagnostics.
• Emerging high-throughput and cell-free RCT assays show promise for future clinical applications.

Conclusions:

• The true benefits of HDL in cardiovascular health may be better understood using novel, high-throughput RCT assays.
• New RCT assays could serve as screening tools for novel therapeutic agents.
• These advanced assays may also function as novel biomarkers for cardiovascular disease risk assessment.