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Updated: Jun 4, 2026
Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein
Published on: October 12, 2017
HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms
Mohamad Navab1, Srinivasa T Reddy, Brian J Van Lenten
1Department of Medicine, David Geffen School of Medicine, UCLA, 10833 Le Conte Avenue, Los Angeles, CA 90095-1679, USA. mnavab@mednet.ucla.edu
Insights
High-density lipoprotein (HDL) cholesterol levels don't always predict cardiovascular risk. Measuring HDL function, not just levels, is crucial for understanding its role in cholesterol transport and inflammation.
Area of Science:
- Biochemistry
- Cardiovascular Science
- Immunology
Background:
- High-density lipoprotein (HDL) plays key roles in reverse cholesterol transport and inflammation modulation.
- HDL-cholesterol levels correlate inversely with cardiovascular event risk, but this measure is insufficient for risk prediction.
- Many individuals with cardiovascular events have normal or high HDL-cholesterol levels, indicating limitations of current metrics.
Purpose of the Study:
- To highlight the limitations of measuring HDL-cholesterol levels for predicting cardiovascular risk.
- To emphasize the importance of HDL composition and function over mere cholesterol levels.
- To advocate for the development of assays that assess HDL functionality.
Main Methods:
- Review of epidemiological studies on HDL-cholesterol and cardiovascular events.
- Analysis of the role of apolipoprotein A-I (apo A-I) in HDL function and cholesterol efflux via ABCA1.
- Examination of how oxidative stress and acute-phase responses modify HDL protein components, impacting its inflammatory potential.
Main Results:
- HDL-cholesterol levels do not accurately reflect HDL composition or its functional capacity.
- Oxidative modification of apo A-I impairs its cholesterol efflux capability.
- Modified HDL particles can shift from an anti-inflammatory to a pro-inflammatory state.
- Preclinical studies show apo A-I mimetic peptides can improve HDL function and reduce atherosclerosis without changing HDL-cholesterol levels.
Conclusions:
- Current measurement of HDL-cholesterol is inadequate for clinical risk assessment.
- HDL function, influenced by its protein components and their modifications, is a critical determinant of its atheroprotective effects.
- Development of robust assays to measure HDL function is essential for supplementing HDL-cholesterol measurements in clinical practice.
Abstract:
The lipoprotein HDL has two important roles: first, it promotes reverse cholesterol transport, and second, it modulates inflammation. Epidemiological studies show that HDL-cholesterol levels are inversely correlated with the risk of cardiovascular events. However, many patients who experience a clinical event have normal, or even high, levels of HDL cholesterol. Measuring HDL-cholesterol levels provides information about the size of the HDL pool, but does not predict HDL composition or function. The main component of HDL, apolipoprotein A-I (apo A-I), is largely responsible for reverse cholesterol transport through the macrophage ATP-binding cassette transporter ABCA1. Apo A-I can be damaged by oxidative mechanisms, which render the protein less able to promote cholesterol efflux. HDL also contains a number of other proteins that are affected by the oxidative environment of the acute-phase response. Modification of the protein components of HDL can convert it from an anti-inflammatory to a proinflammatory particle. Small peptides that mimic some of the properties of apo A-I have been shown in preclinical models to improve HDL function and reduce atherosclerosis without altering HDL-cholesterol levels. Robust assays to evaluate the function of HDL are needed to supplement the measurement of HDL-cholesterol levels in the clinic.
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