Profound resolution of early atherosclerosis with conjugated linoleic acid.
Conjugated linoleic acid (CLA) refers to a group of positional and geometric isomers of linoleic acid and has been shown to suppress the development of atherosclerosis in experimental models. However, the mechanism involved is unclear although it is believed it may act as a cyclooxygenase inhibitor or as an agonist of the nuclear receptors, peroxisome proliferator activated receptors (PPARs). In this study, we examined the effect of cis-9,trans-11:trans-10,cis-12-CLA (80:20 blend) on the regression of pre-established atherosclerosis. ApoE(-/-) mice fed a 1% cholesterol diet were randomized at 8 weeks to continue receiving the diet supplemented with 1% control saturated fat or 1% CLA blend for a further 8 weeks. CLA supplementation did not simply prevent progression but induced almost complete resolution of atherosclerosis. Although CLA inhibited platelet deposition, as detected by staining of platelet glycoprotein alpha11b beta111a, it did not inhibit COX-mediated generation of prostaglandins in this model. However, PPARalpha and PPARgamma expression was increased in the aorta of the CLA-treated animals. This was coincident with decreased macrophage accumulation and decreased expression of the macrophage scavenger receptor CD36 and increased apoptosis in the aorta in vivo. CLA induces the resolution of atherosclerosis by negatively regulating the expression of pro-inflammatory genes and inducing apoptosis in the atherosclerotic lesion.
Toomey
Sinead
S
Department of Clinical Pharmacology and Institute of Biopharmaceutical Sciences, Royal College of Surgeons, Dublin, Ireland.
Harhen
Brendan
B
Roche
Helen M
HM
Fitzgerald
Desmond
D
Belton
Orina
O
D000818:Animals; D001011:Aorta / Q000378:metabolism; D017209:Apoptosis; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D015777:Eicosanoids / Q000652:urine; D011464:Epoprostenol / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D015777:Eicosanoids; D044243:Linoleic Acids, Conjugated; D047492:Peroxisome Proliferator-Activated Receptors; D013931:Thromboxanes; D014280:Triglycerides; D002784:Cholesterol; D011464:Epoprostenol