Liposomes enriched in oleic acid are less susceptible to oxidation and have less proinflammatory activity when exposed to oxidizing conditions.
As there is frequently a reciprocal relationship between oleic acid and linoleic acid content in LDL after dietary supplementation, it is difficult to determine the independent effects of oleic and linoleic acid on LDL oxidation. It is also unknown whether monounsaturated fatty acid enrichment might reduce the generation of proinflammatory products that occur when the polyunsaturated fatty acid-rich phospholipids within lipoproteins undergo mild oxidation. To address these issues, we exposed liposomes containing variable amounts of oleic, linoleic, and arachidonic acid to oxidizing conditions. Liposomes enriched in oleic acid but with constant amounts of linoleic acid were less susceptible to oxidation and had significantly greater lag times and time to half maximum conjugated diene formation. When mildly oxidized, liposomes containing either linoleic acid or arachadonic acid increased monocyte chemotaxis and monocyte adhesion to endothelial cells nearly 5-fold, demonstrating that oxidation products of both these polyunsaturated fatty acids are bioactive. The addition of a platelet activating factor receptor antagonist to endothelial cells inhibited stimulation of monocyte adhesion by oxidized liposomes, suggesting that some bioactive oxidation products of polyunsaturated fatty acids may resemble platelet activating factor in structure. In contrast, when liposomes were enriched in oleic acid, monocyte chemotaxis and monocyte adhesion were nearly completely inhibited. These results suggest that enriching lipoproteins with oleic acid may reduce oxidation both by a direct "antioxidant"-like effect and by reducing the amount of linoleic acid available for oxidation as well as reduce the generation of bioactive particles that occur during mild oxidation.
Lee
C
C
Department of Medicine, University of California, San Diego, La Jolla 92093-0682, USA.
Barnett
J
J
Reaven
P D
PD
D000818:Animals; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D019301:Oleic Acid / Q000737:chemistry* / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry* / Q000494:pharmacology
D008081:Liposomes; D010713:Phosphatidylcholines; D019301:Oleic Acid; D001093:Arachidonate 15-Lipoxygenase