Genetic control of the inflammatory response induced by oxidized lipids.
The fatty streak begins with entrapment of apolipoprotein B (apoB)-containing lipoproteins in the subendothelial space at susceptible sites in the arterial wall. Minimally oxidized low density lipoprotein (MM-LDL) induces endothelial cells to bind monocytes and produce message and protein for monocyte chemotactic protein-1 and macrophage colony-stimulating factor. In culture, human endothelial and smooth muscle cells in arterial wall configuration sequester LDL, protecting it from antioxidants and giving rise to MM-LDL-like species. In mice, MM-LDL induces monocyte binding at susceptible aortic sites; the monocytes may then differentiate into macrophages that release reactive oxygen and active aldehydes, resulting in highly oxidized LDL leading to foam cell formation. Feeding mice an atherogenic diet induces expression of several inflammatory and oxidative stress genes, including serum amyloid A, which binds exclusively to HDL. This may contribute to a decrease in protective HDL levels seen in mice susceptible to fatty streak formation.
Liao
F
F
Department of Medicine, University of California, School of Medicine, Los Angeles 90024-1679.
Andalibi
A
A
Lusis
A J
AJ
Fogelman
A M
AM
D000818:Animals; D001158:Arteries / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D001167:Arteritis / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008055:Lipids / Q000235:genetics*; D051379:Mice; D018384:Oxidative Stress
D008055:Lipids