Dysfunctional high-density lipoprotein and atherosclerosis

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• High-density lipoprotein (HDL) is a known negative risk factor for atherosclerosis and coronary artery disease.
• HDL exerts protective effects through multiple pathophysiologic mechanisms, including reverse cholesterol transport.
• Low-density lipoprotein (LDL) can contribute to atherosclerosis by forming lipid-laden foam cells.

Purpose of the Study:

• To explore the multifaceted mechanisms by which HDL mitigates atherosclerotic burden.
• To investigate the additional beneficial physiological effects of HDL beyond cholesterol transport.
• To address the paradox of significant atherosclerotic burden despite normal or elevated HDL levels.

Main Methods:

• Review of epidemiological, pathological, and experimental studies on HDL function.
• Analysis of HDL's interaction with foam cells and cholesterol removal pathways.
• Examination of HDL's impact on endothelial function, inflammation, and oxidative stress.

Main Results:

• HDL removes cholesterol from peripheral cells via receptor-mediated processes and ATP binding cassettes.
• HDL enhances endothelial function, possesses anti-inflammatory and antioxidant properties, and influences prostacyclin production.
• Dysfunctional HDL, observed in conditions of inflammation and oxidative stress, can be improved through lifestyle changes and pharmacologic interventions.

Conclusions:

• HDL plays a crucial role in preventing atherosclerosis through diverse mechanisms.
• Impaired HDL functionality due to inflammation and oxidative stress is a significant clinical concern.
• Novel therapeutic strategies, including orally active mimetic proteins, show promise for restoring HDL function.