Effect of atorvastatin on atherosclerotic plaque formation and platelet activation in hypercholesterolemic rats


GÖÇMEN A. Y., OCAK G. A., ÖZBİLİM G., Delibas N., GÜMÜŞLÜ S.

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, vol.91, no.9, pp.680-685, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 91 Issue: 9
  • Publication Date: 2013
  • Doi Number: 10.1139/cjpp-2012-0325
  • Journal Name: CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.680-685
  • Keywords: statin, hypercholesterolemia, platelet activation, P-selectin, CD40, CD40L, CORONARY-ARTERY, MICE, INTERLEUKIN-6, SIMVASTATIN, PRAVASTATIN, EXPRESSION, SYSTEM, RISK, CD40
  • Akdeniz University Affiliated: Yes

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.