Inflammation alters HDL composition and function: implications for HDL-raising therapies

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Proteomics

Background:

• Plasma high-density lipoprotein (HDL)-cholesterol levels are established predictors of cardiovascular disease (CVD) risk.
• Recent drug trial failures and genetic studies question the utility of HDL-cholesterol as a sole risk marker.
• Emerging evidence suggests HDL composition and function are more critical than cholesterol levels for antiatherogenic properties.

Purpose of the Study:

• To investigate the role of HDL composition and function in cardiovascular risk.
• To explore novel therapeutic targets beyond simply raising HDL-cholesterol levels.
• To enhance the identification of individuals at increased cardiovascular risk.

Main Methods:

• Analysis of HDL protein composition using mass spectrometry.
• Comparison of HDL from high-risk patients and atherosclerotic tissue with healthy controls.
• Assessment of HDL functionality in relation to cardiovascular risk.

Main Results:

• HDL protein composition is complex and significantly altered in high-risk cardiovascular patients.
• Alterations in HDL composition and function were observed in HDL isolated from atherosclerotic tissue.
• Steady-state HDL-cholesterol concentrations may offer limited insight into HDL's antiatherogenic capacity.

Conclusions:

• HDL composition and function, rather than cholesterol levels, are crucial determinants of its antiatherogenic properties.
• Targeting HDL functionality offers a promising avenue for novel CVD therapies.
• Assessing HDL composition and function can improve cardiovascular risk stratification.