Antiatherogenic function of HDL particle subpopulations: focus on antioxidative activities

Area of Science:

• Cardiovascular Science
• Lipid Metabolism
• Oxidative Stress Biology

Background:

• Oxidative stress promotes atherosclerosis by generating pro-atherogenic oxidized low-density lipoprotein (oxLDL).
• High-density lipoprotein (HDL) particles, especially HDL3, protect LDL from oxidative damage in the arterial intima.
• This protection inhibits the formation of inflammatory oxidized lipids like lipid hydroperoxides (LOOH) and oxidized phospholipids (oxPL).

Purpose of the Study:

• To elucidate the mechanisms of HDL-mediated protection against LDL oxidation.
• To investigate the role of HDL composition and function in atherogenic dyslipidaemias.
• To explore therapeutic strategies targeting HDL for cardiovascular disease prevention.

Main Methods:

• Investigated HDL's role in inactivating lipid hydroperoxides (LOOH) through phospholipid hydroperoxide (PLOOH) transfer and reduction by apolipoprotein A-I (apoA-I).
• Examined the contribution of HDL-associated enzymes to the inactivation of oxidized phospholipids (oxPL).
• Analyzed HDL proteome and lipidome in dyslipidaemic patients to identify functional deficiencies.

Main Results:

• HDL inactivates LOOH via PLOOH transfer to HDL3 and reduction by apoA-I's methionine residues, forming phospholipid hydroxides (PLOH).
• HDL-associated enzymes contribute to oxPL hydrolysis.
• Antioxidative activity of HDL is impaired in dyslipidaemia due to altered HDL particle composition and increased surface rigidity.

Conclusions:

• HDL plays a critical role in preventing LDL oxidation and subsequent atherosclerosis.
• Defective HDL antioxidative function in dyslipidaemia contributes to cardiovascular risk.
• Therapeutic strategies normalizing HDL metabolism, composition, and function show promise for treating atherosclerosis.