Regression of pre-established atherosclerosis in the apoE-/- mouse by conjugated linoleic acid.
Conjugated linoleic acid (CLA) refers to a group of positional and geometric isomers of linoleic acid that has been shown to suppress the development of atherosclerosis in a rabbit model. We investigated whether CLA acts as a cyclo-oxygenase (COX) inhibitor or as an agonist of the peroxisome-proliferator-activator receptor (PPAR) gamma in the ApoE(-/-) mouse model. In vitro, a 9-cis, 11-trans isomer of CLA inhibited prostaglandin formation and oxygen consumption by both isoforms of COX, with no evidence by MS of alternative products being generated. In vivo, supplementation with CLA was found to induce resolution of atherosclerosis. The effect of CLA in vivo could not be explained by COX inhibition alone, as urinary prostaglandin levels were unchanged in animals receiving CLA supplementation, and administration of selective COX inhibitors did not induce lesion regression. There was however induction of PPAR gamma, a known response to agonists of this nuclear orphan receptor.
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015777:Eicosanoids / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D019787:Linoleic Acid / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008954:Models, Biological; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D001057:Apolipoproteins E; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011453:Prostaglandins; D020033:Protein Isoforms; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D019787:Linoleic Acid; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse