HDL and the inflammatory response induced by LDL-derived oxidized phospholipids.
Oxidation of low density lipoprotein (LDL) phospholipids containing arachidonic acid at the sn-2 position occurs when a critical concentration of "seeding molecules" derived from the lipoxygenase pathway is reached in LDL. When this critical concentration is reached, the nonenzymatic oxidation of LDL phospholipids produces a series of biologically active, oxidized phospholipids that mediate the cellular events seen in the developing fatty streak. Normal high density lipoprotein (HDL) contains at least 4 enzymes as well as apolipoproteins that can prevent the formation of the LDL-derived oxidized phospholipids or inactivate them after they are formed. In the sense that normal HDL can prevent the formation of or inactivate these inflammatory LDL-derived oxidized phospholipids, normal HDL is anti-inflammatory. HDL from mice that are genetically predisposed to diet-induced atherosclerosis became proinflammatory when the mice are fed an atherogenic diet, injected with LDL-derived oxidized phospholipids, or infected with influenza A virus. Mice that were genetically engineered to be hyperlipidemic on a chow diet and patients with coronary atherosclerosis, despite normal lipid levels, also had proinflammatory HDL. It is proposed that LDL-derived oxidized phospholipids and HDL may be part of a system of nonspecific innate immunity and that the detection of proinflammatory HDL may be a useful marker of susceptibility to atherosclerosis.
Navab
M
M
Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095-1736, USA.
Berliner
J A
JA
Subbanagounder
G
G
Hama
S
S
Lusis
A J
AJ
Castellani
L W
LW
Reddy
S
S
Shih
D
D
Shi
W
W
Watson
A D
AD
Van Lenten
B J
BJ
Vora
D
D
Fogelman
A M
AM
D000818:Animals; D001161:Arteriosclerosis / Q000175:diagnosis / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000378:metabolism / Q000503:physiopathology; D004036:Diet, Atherogenic; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D008075:Lipoproteins, HDL / Q000378:metabolism* / Q000502:physiology; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000502:physiology; D008084:Lipoxygenase / Q000378:metabolism / Q000502:physiology; D051379:Mice; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism* / Q000502:physiology
D015415:Biomarkers; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; C099252:oxidized low density lipoprotein; D008084:Lipoxygenase