Oxidized lipids as mediators of coronary heart disease.
OBJECTIVE
To summarize the recent evidence on the physiological relevance of the view that LDL lipid oxidation may play a major role in the inflammatory reaction that leads to or amplifies atherogenesis. Oxidation of 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. This generates a series of biologically active, oxidized phospholipids that mediate the cellular events seen in the developing fatty streak.


RESULTS
We have observed that LDL from mice that are genetically predisposed to diet-induced atherosclerosis is highly proinflammatory when the mice are maintained on an atherogenic diet, when they are injected with LDL-derived oxidized phospholipids, or once they are infected with influenza A virus. Patients with coronary atherosclerosis also had highly proinflammatory LDL, despite having normal blood lipid levels or normal plasma HDL levels.


CONCLUSIONS
We and others have hypothesized that HDL and LDL-derived oxidized phospholipids may be part of a system of nonspecific innate immunity. We therefore propose that determination of HDL capacity against LDL oxidation and the detection of proinflammatory HDL may be a useful marker of susceptibility to atherosclerosis.
Navab
Mohamad
M
Department of Medicine, Cardiology, University of California Los Angeles, 90095-1679, USA. mnavab@mednet.ucla.edu
Hama
Susan Y
SY
Reddy
Srinu T
ST
Ng
Carey J
CJ
Van Lenten
Brian J
BJ
Laks
Hillel
H
Fogelman
Alan M
AM
Ready
Srinu T
ST
D000818:Animals; D018797:Cell Cycle Proteins; D003327:Coronary Disease / Q000378:metabolism*; D054638:Dual Specificity Phosphatase 1; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases