HDL and the inflammatory response induced by LDL-derived oxidized phospholipids

Area of Science:

• Biochemistry
• Immunology
• Cardiovascular Science

Background:

• Oxidation of low-density lipoprotein (LDL) phospholipids, particularly those with arachidonic acid at the sn-2 position, is initiated by lipoxygenase-derived seeding molecules.
• This oxidation generates biologically active oxidized phospholipids that drive cellular events in early atherosclerosis (fatty streak formation).

Purpose of the Study:

• To investigate the role of high-density lipoprotein (HDL) in the formation and inactivation of LDL-derived oxidized phospholipids.
• To explore the potential of HDL to transition from an anti-inflammatory to a proinflammatory state and its implications for atherosclerosis.

Main Methods:

• The study examines the enzymatic and apolipoprotein content of normal HDL and its capacity to inhibit LDL oxidation.
• It investigates HDL's inflammatory status in mouse models of diet-induced atherosclerosis and hyperlipidemia, as well as in patients with coronary atherosclerosis.

Main Results:

• Normal HDL possesses anti-inflammatory properties by preventing LDL oxidation or inactivating oxidized phospholipids.
• HDL from mice on atherogenic diets, or those exposed to oxidized LDL or influenza A virus, becomes proinflammatory.
• Proinflammatory HDL was also observed in hyperlipidemic mice and human patients with coronary atherosclerosis, irrespective of lipid levels.

Conclusions:

• LDL-derived oxidized phospholipids and HDL may function within the innate immune system.
• The presence of proinflammatory HDL could serve as a valuable biomarker for predicting atherosclerosis susceptibility.