Oxidized Lipids
The oxidation of low density lipoproteins (LDL) has been correlated with atherogenesis through a variety of pathways. One of the oxidative processes involves breakdown and modification of the intrinsic lipids and protein and leads to macrophage recognition and uptake of the oxidized LDL (OxLDL). We have chemically synthesized and fully characterized several unique oxidized phospholipids (OxPL). Synthetic adducts of oxidized phospholipids effectively blocked the binding and uptake of OxLDL by mouse peritoneal macrophages (213)and inhibited phagocytosis of apopotic cells by macrophages (214). Furthermore, they blocked the uptake of OxLDL by cells transfected with CD36 (228). Oxidized fatty acids are found predominantly as components of phospholipids, which can be released by phospholipase A2 (PLA2). We have now initiated studies aimed at identifying the PLA2's involved in their hydrolysis and the role of OxPL in generating epitopes on OxLDL for recognition of macrophage scavenger receptors, and we have recently discovered that Schiff base formation and aldol condensates are key to oxidized lipid effects (239).
The oxidation of low density lipoproteins (LDL) has been correlated with atherogenesis through a variety of pathways. One of the oxidative processes involves breakdown and modification of the intrinsic lipids and protein and leads to macrophage recognition and uptake of the oxidized LDL (OxLDL). We have chemically synthesized and fully characterized several unique oxidized phospholipids (OxPL). Synthetic adducts of oxidized phospholipids effectively blocked the binding and uptake of OxLDL by mouse peritoneal macrophages (213)and inhibited phagocytosis of apopotic cells by macrophages (214). Furthermore, they blocked the uptake of OxLDL by cells transfected with CD36 (228). Oxidized fatty acids are found predominantly as components of phospholipids, which can be released by phospholipase A2 (PLA2). We have now initiated studies aimed at identifying the PLA2's involved in their hydrolysis and the role of OxPL in generating epitopes on OxLDL for recognition of macrophage scavenger receptors, and we have recently discovered that Schiff base formation and aldol condensates are key to oxidized lipid effects (239).