title: Effect of atorvastatin on atherosclerotic plaque formation and platelet activation in hypercholesterolemic rats.
abstract: We aimed to investigate whether atorvastatin influenced the CD40-CD40L pathway in atherosclerosis formation in rats fed a high cholesterol diet. Thirty-six male Wistar rats were divided among 4 groups as follows: control (C), statin (S), 5% cholesterol fed (HC), and statin-administered hypercholesterolemic (HCS). Serum levels of lipids, soluble CD40L, platelet factor 4, and interleukin-6 were assayed with commercial kits. The number of platelets expressing surface P-selectin, CD40, and CD40L were determined by flow cytometry. Aortas were examined for fatty streaks. In the HC group, we observed a significant increase in serum lipid levels and platelet activation markers compared with the control group. Rats in the HCS group had a significant decrease in lipid levels and downregulation in the number of platelets expressing surface P-selectin, CD40, and CD40L compared with the HC group. We observed decreased fatty streak formations in aortas in HCS rats. A positive correlation was found for platelet activation markers and atherosclerotic fatty streak formations. Regression analysis revealed that the predictor of atherosclerosis was CD40L. Our study suggests that in a rat hypercholesterolemic model, statin treatment may influence the CD40-CD40L dyad, and that this effect is parallelled by a suppression of progression of atherosclerotic plaque formation.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Bozok University, 66200 Yozgat, Turkey.
authors.forename: Ayse Yesim
authors.initials: AY
authors.lastname: Gocmen
authors.forename: Guzide Ayse
authors.initials: GA
authors.lastname: Ocak
authors.forename: Gulay
authors.initials: G
authors.lastname: Ozbilim
authors.forename: Namik
authors.initials: N
authors.lastname: Delibas
authors.forename: Saadet
authors.initials: S
authors.lastname: Gumuslu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D019013:CD40 Antigens / Q000097:blood; D023201:CD40 Ligand / Q000097:blood; D002791:Cholesterol, Dietary; D004195:Disease Models, Animal; D018450:Disease Progression; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D019007:P-Selectin / Q000097:blood; D058226:Plaque, Atherosclerotic; D015539:Platelet Activation / Q000187:drug effects*; D010978:Platelet Factor 4 / Q000097:blood; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D019013:CD40 Antigens; D002791:Cholesterol, Dietary; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D008055:Lipids; D019007:P-Selectin; D011758:Pyrroles; D023201:CD40 Ligand; D010978:Platelet Factor 4; D000069059:Atorvastatin