HDL and arteriosclerosis: beyond reverse cholesterol transport

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Atherosclerosis Research

Background:

• Inverse correlation between HDL cholesterol and coronary heart disease risk.
• HDL metabolism is a target for pharmacological intervention in atherosclerosis.
• Previous review covered reverse cholesterol transport and classic HDL anti-atherogenic function.

Purpose of the Study:

• Summarize current understanding of additional biological, potentially anti-atherogenic properties of HDL.
• Highlight the complexity of HDL's anti-atherogenic mechanisms.
• Emphasize HDL functionality over plasma levels for therapeutic impact.

Main Methods:

• Literature review and synthesis of existing research on HDL properties.
• Analysis of in vitro and in vivo studies on HDL's biological activities.
• Examination of HDL components responsible for various functions.

Main Results:

• HDL inhibits monocyte chemotaxis, leukocyte adhesion, endothelial dysfunction, apoptosis, LDL oxidation, complement activation, platelet activation, and factor X activation.
• HDL stimulates endothelial and smooth muscle cell proliferation, prostacyclin and natriuretic peptide C synthesis, and protein C and S activation.
• These diverse activities include anti-inflammatory, anti-oxidative, anti-aggregatory, anti-coagulant, and pro-fibrinolytic effects.
• Different HDL components (apolipoproteins, enzymes, phospholipids) mediate these functions.

Conclusions:

• HDL possesses numerous anti-atherogenic properties beyond cholesterol transport.
• HDL's complex functions are mediated by various components.
• Therapeutic strategies should focus on enhancing HDL functionality, not just cholesterol levels.