Protective effect of BN 52021, a specific antagonist of platelet-activating factor (PAF-acether) against diet-induced cholesteryl ester deposition in rabbit aorta.
Platelet-activating factor (PAF-acether), a phospholipid mediator involved in inflammatory reactions, has been reported to induce endovascular surface lesions. We investigated the possible involvement of PAF-acether in the mechanism of arterial cholesterol deposition. Rabbits fed a normal or hypercholesterolic diet were treated orally for 1 month with BN 52021 (20 mg/kg per day), a specific PAF-acether antagonist, and killed at the end of treatment. Cholesterol feeding resulted in a marked (50-fold) increase in plasma cholesterol. However, the drug had no significant effect on the diet-induced hypercholesterolemia. Free and esterified cholesterol were markedly increased (635%) in the aorta of animals receiving the atherogenic diet. This accumulation was reduced by 36% upon simultaneous administration of BN 52021 (P less than 0.02, n = 15). This decrease essentially affected the esterified cholesterol content. Conversely, BN 52021 showed no effect on the cellular cholesterol esterification, since liver acyl-CoA: cholesterol acyltransferase activity remained unchanged. This study indicates that BN 52021 is effective in reducing cholesterol accumulation in rabbit atherosclerotic aorta, without changing the plasma cholesterol levels.
INSERM Unité 101, Hôpital Purpan, Toulouse, France.
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Feliste
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Perret
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Braquet
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Chap
D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001161:Arteriosclerosis / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D002788:Cholesterol Esters / Q000378:metabolism*; D004036:Diet, Atherogenic; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones / Q000494:pharmacology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors*; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D002788:Cholesterol Esters; D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; D002784:Cholesterol; C045856:ginkgolide B; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase