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Updated: Mar 11, 2026

High-Density Lipoprotein-Specific Phospholipid Efflux Assay
Published on: September 30, 2025
The Changing Face of HDL and the Best Way to Measure It
Sotirios K Karathanasis1, Lita A Freeman2, Scott M Gordon2
1Cardiovascular and Metabolic Disease Section, MedImmune, Gaithersburg, MD.
Insights
High-density lipoprotein cholesterol (HDL-C) is a cardiovascular health biomarker. Beyond cholesterol transport, HDL offers numerous cardioprotective effects, prompting research into new diagnostic assays.
Area of Science:
- Lipidology
- Cardiovascular Research
- Biomarker Development
Background:
- High-density lipoprotein cholesterol (HDL-C) is a key lipid biomarker for cardiovascular health assessment.
- While HDL's role in reverse cholesterol transport (RCT) is established, its broader cardioprotective functions are increasingly recognized.
- Novel assays are emerging to evaluate diverse HDL functions, potentially leading to new diagnostic tools.
Purpose of the Study:
- To review the current understanding of HDL particle formation and maturation through RCT.
- To explore the non-RCT-related cardioprotective roles of HDL, including antioxidative, anti-inflammatory, and vasoprotective effects.
- To discuss methodologies for assessing HDL function and the potential for new diagnostic assays based on HDL composition.
Main Methods:
- Literature review of HDL formation, maturation, and function.
- Analysis of existing and emerging methodologies for assessing HDL functions.
- Discussion of HDL's protein and lipid composition in health and disease.
Main Results:
- HDL possesses multiple cardioprotective properties beyond RCT, such as antioxidative, anti-inflammatory, antiapoptotic, antithrombotic, anti-infective, and vasoprotective effects.
- The composition of HDL particles (proteins and lipids) is crucial for its function in both health and disease.
- Current methods for assessing HDL function are evolving, with potential for new diagnostic applications.
Conclusions:
- Epidemiological studies consistently link lower HDL-C to increased cardiovascular disease risk.
- Clinical and experimental data on HDL-C's direct antiatherogenic role remain inconsistent.
- Translating the expanded understanding of HDL biology into effective therapies requires developing new methods to measure HDL beyond its cholesterol content.
Background:
HDL cholesterol (HDL-C) is a commonly used lipid biomarker for assessing cardiovascular health. While a central focus has been placed on the role of HDL in the reverse cholesterol transport (RCT) process, our appreciation for the other cardioprotective properties of HDL continues to expand with further investigation into the structure and function of HDL and its specific subfractions. The development of novel assays is empowering the research community to assess different aspects of HDL function, which at some point may evolve into new diagnostic tests.
Content:
This review discusses our current understanding of the formation and maturation of HDL particles via RCT, as well as the newly recognized roles of HDL outside RCT. The antioxidative, antiinflammatory, antiapoptotic, antithrombotic, antiinfective, and vasoprotective effects of HDL are all discussed, as are the related methodologies for assessing these different aspects of HDL function. We elaborate on the importance of protein and lipid composition of HDL in health and disease and highlight potential new diagnostic assays based on these parameters.
Summary:
Although multiple epidemiologic studies have confirmed that HDL-C is a strong negative risk marker for cardiovascular disease, several clinical and experimental studies have yielded inconsistent results on the direct role of HDL-C as an antiatherogenic factor. As of yet, our increased understanding of HDL biology has not been translated into successful new therapies, but will undoubtedly depend on the development of alternative ways for measuring HDL besides its cholesterol content.
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