Inflammation Oxidized phospholipids

Leitinger N. (2003). Oxidized phospholipids as modulators of inflammation in atherosclerosis. Curr. Opin. Lipidol. 14 421 130. 

Nonas, S., Miller, I., Kawkitinarong, K., Chatchavalvanich, S., Gorshkova, I., Bochkov, V.N., Leitinger, N., Natarajan, V., Garcia, J.G., and Birukov, K.G. (2006). Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. Am J Respir Crit Care Med 173, 1130-8. 

Abstract Since the discovery of oxidized phospholipids (OxPL) and their implication as modulators of inflammation in cardiovascular disease, roles for these lipid oxidation products have been suggested in many other disease settings. Lipid oxidation products accumulate in inflamed and oxidatively damaged tissue, where they are derived from oxidative modification of lipoproteins, but also from membranes of cells undergoing apoptosis. Thus, increased oxidative stress as well as decreased clearance of apoptotic cells has been implied to contribute to accumulation of OxPL in chronically inflamed tissues. 

Fumkranz, A. et al. Oxidized phospholipids trigger atherogenic inflammation in murine arteries. Arteriosclerosis, Thrombosis, and Vascular Biology 25 (2005) 633-8. 

Leitinger, N. Oxidized phospholipids as triggers of inflammation in atherosclerosis. Mol. Nutr. Food Res. 49 (2005) 1063-71. 

Nonas, S. et al. Oxidized phospholipids reduce ventilator-induced vascular leak and inflammation in vivo. Critical Care, 12(1) R27, 2008. 

Kadi, A. Sharma, P. R. Chen, W. Agrawal, R. Meher, A. K. Rudraiah, S. Grubbs, N. Sharaia, R. Leitinger, N., Oxidized phospholipid-induced inflammation is mediated by Toll-like receptor 2. Free Radio Biol Med 2011, 51(10), 1903-9. 

Greig, F.H., Kennedy, S., and Spickett, C.M. 2012. Physiological effects of oxidized phospholipids and their cellular signaling mechanisms in inflammation. Free Radic. Biol. Med.. 52, 266-280. 

Hainzl, E., Demyanets, S. et al. 2010. Oxidized phospholipids are more potent antagonists of lipopolysaccharide than inducers of inflammation, 185,7706-7712. 

Another form of tissue damage is induced by increased oxidative stress. Since oxidative tissue damage is a primary feature of chronic inflammation, we propose that oxidatively modified lipids (such as oxidized phospholipids) represent DAMPs that elicit specific immune responses via PRRs including TLRs. 

Kadi, A. et al. Oxidized phospholipid-induced inflammation is mediated by ToU-like receptor 2. Free Radic. Biol. Med. 51, 1903-9, 2011. 

Dietary intake of n-6 fatty acids such as linoleic acid, and n-3 fatty acids, such as the fish oils eicosapentanoic acid and docosahexaenoic acid, lowers plasma cholesterol and antagonizes platelet activation, but the fish oils are much more potent in this regard [26]. In particular, n-3 fatty acids competitively inhibit thromboxane synthesis in platelets but not prostacyclin synthesis in endothelial cells. These fatty acids have also been shown to have other potentially anti-atherogenic effects, such as inhibition of monocyte cytokine synthesis, smooth muscle cell proliferation, and monocyte adhesion to endothelial cells. While dietary intake of n-3 fatty acid-rich fish oils appears to be atheroprotective, human and animal dietary studies with the n-6 fatty acid linoleic acid have yielded conflicting results in terms of effects on both plasma lipoproteins and atherosclerosis. Indeed, excess amounts of both n-3 and n-6 fatty acids may actually promote oxidation, inflammation, and possibly atherogenesis (M. Toberek, 1998). In this context, enzymatic and non-enzymatic oxidation of linoleic acid in the sn-2 position of LDL phospholipids to 9- and 13-hydroxy derivatives is a key event in LDL oxidation (Section 6.2). 

Mcintyre, T. M. 2012. Bioactive oxidatively truncated phospholipids in inflammation and apoptosis Formation, targets, and inactivation. 1818,... 

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