Dysfunctional High-Density Lipoprotein: An Innovative Target for Proteomics and Lipidomics

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Molecular Biology

Background:

• High-Density Lipoprotein-Cholesterol (HDL-C) is traditionally viewed as protective against cardiovascular disease.
• However, some genetic conditions with low HDL-C do not show premature atherosclerosis, questioning its predictive value.
• HDL's beneficial effects may depend on quality and subfractions, not just concentration.

Purpose of the Study:

• To explore the heterogeneity of HDL and its impact on cardiovascular disease.
• To investigate how chronic inflammation affects HDL functionality.
• To highlight the role of proteomics and lipidomics in understanding HDL dysfunction and developing therapies.

Main Methods:

• Analysis of HDL subfractions and their protein-lipid composition.
• Investigation of HDL alterations in chronic inflammatory conditions.
• Application of proteomics and lipidomics for molecular profiling.

Main Results:

• HDL's protective functions are compromised in inflammatory environments.
• Dysfunctional HDL can become proatherogenic, prooxidant, and proinflammatory.
• Distinct HDL subfractions possess unique physiological and pathophysiological roles.

Conclusions:

• HDL-C concentration alone is an insufficient predictor of cardiovascular disease risk.
• HDL quality and subfraction composition are critical determinants of its function.
• Proteomics and lipidomics are essential for elucidating HDL dysfunction and identifying new therapeutic targets for cardiovascular disease.