Inflammation-related gene expression by lipid oxidation-derived products in the progression of atherosclerosis.
Vascular areas of atherosclerotic development persist in a state of inflammation, and any further inflammatory stimulus in the subintimal area elicits a proatherogenic response; this alters the behavior of the artery wall cells and recruits further inflammatory cells. In association with the inflammatory response, oxidative events are also involved in the development of atherosclerotic plaques. It is now unanimously recognized that lipid oxidation-derived products are key players in the initiation and progression of atherosclerotic lesions. Oxidized lipids, derived from oxidatively modified low-density lipoproteins (LDLs), which accumulate in the intima, strongly modulate inflammation-related gene expression, through involvement of various signaling pathways. In addition, considerable evidence supports a proatherogenic role of a large group of potent bioactive lipids called eicosanoids, which derive from oxidation of arachidonic acid, a component of membrane phospholipids. Of note, LDL lipid oxidation products might regulate eicosanoid production, modulating the enzymatic degradation of arachidonic acid by cyclooxygenases and lipoxygenases; these enzymes might also directly contribute to LDL oxidation. This review provides a comprehensive overview of current knowledge on signal transduction pathways and inflammatory gene expression, modulated by lipid oxidation-derived products, in the progression of atherosclerosis.
Department of Clinical and Biological Sciences, University of Torino, Torino, Italy.
Gabriella
G
Leonarduzzi
Paola
P
Gamba
Simona
S
Gargiulo
Fiorella
F
Biasi
Giuseppe
G
Poli
D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology; D015777:Eicosanoids / Q000378:metabolism; D004730:Endothelium, Vascular; D005609:Free Radicals; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D058226:Plaque, Atherosclerotic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction
D015777:Eicosanoids; D005609:Free Radicals; D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species