Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

Area of Science:

• Cardiovascular Research
• Lipid Metabolism
• Molecular Biology

Background:

• Low plasma high-density lipoprotein (HDL) cholesterol levels are linked to increased coronary heart disease risk.
• HDL plays a crucial role in reverse cholesterol transport and possesses anti-inflammatory and anti-oxidative properties, suggesting atheroprotective functions.
• Despite its importance, targeting HDL for cardiovascular disease prevention and treatment has been unsuccessful, potentially due to oversimplification of its complex nature.

Purpose of the Study:

• To investigate the structural and functional complexity of high-density lipoprotein (HDL) particles.
• To explore the heterogeneity of HDL components, including lipids, proteins, and microRNAs, in both physiological and pathological conditions.
• To identify structure-function relationships of HDL-associated molecules for potential therapeutic and diagnostic applications in atherosclerosis.

Main Methods:

• Systematic analysis of HDL-associated molecules and their modifications.
• Investigation of quantitative and qualitative molecular changes in HDL components under pathological conditions.
• Evaluation of the relative contribution of different HDL components and functions in the pathogenesis of atherosclerosis.

Main Results:

• HDL particles exhibit significant physiological heterogeneity, further amplified in pathological states.
• Molecular changes in HDL components are associated with both loss of normal function and gain of pathological dysfunction.
• Current understanding of HDL's role in atherosclerosis is limited by the complexity of its molecular composition and functions.

Conclusions:

• Targeting HDL cholesterol alone is insufficient for effective cardiovascular disease treatment due to HDL's multifaceted nature.
• Systematic structure-function analyses are necessary to elucidate the precise roles of HDL components in atherosclerosis.
• Identifying specific HDL biomarkers and therapeutic targets could lead to novel strategies for cardiovascular disease management and diagnostics.