Effect of resveratrol on platelet activation in hypercholesterolemia rats: CD40-CD40L system as a potential target

• Published in: Applied physiology, nutrition, and metabolism nutrition, and metabolism, 2011-06, Vol.36 (3), p.323
• Main Authors: Gocmen, Ayse Yesim, Burgucu, Durmus, Gumuslu, Saadet
• Format: Article
• Language: English
• Subjects: Care and treatment; Diagnosis; Enzyme-linked immunosorbent assay; Health aspects; Hypercholesterolemia; Physiological aspects; Resveratrol; Wine
• ISSN: 1715-5312
• DOI: 10.1139/H11-022

Our aim was to investigate whether trans-resveratrol (t-resveratrol), a red wine constituent known for its cardio- protective effects, was able to influence CD40 ligand (CD40L) and its receptor CD40 in platelets of hypercholesterolemic rats. Sixty Wistar rats were divided into 5 groups: control (C), ethanol (E), t-resveratrol (R), hypercholesterolemia (HC), and hypercholesterolemia plus t-resveratrol (HCR). Rats in the C, E, and R groups were fed a normal diet for 80 days. For 20 days before sacrifice, we intraperitoneally (i.p.) administered 0.1 mL ethanol (50% v/v) to the E group, and 0.1 mL t-resveratrol (20 mg x [kg.sup.-1] x [day.sup.1]) to the R group. Rats in the HC and HCR groups were fed a 5% cholesterol diet for 80 days. Rats in the HCR group were administered i.p. 0.1 mL t-resveratrol (20 mg x [kg.sup.-1] x [day.sup.-1]) for 20 days before sacrifice. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), very low-density lipoprotein (VLDL-C), and total triglycerides (TG) were assayed with a commercial colorimetric kit. Platelet P-selectin, CD40, and CD40L expression was determined by flow cytometry. sCD40L and IL6 levels were measured by ELISA. In the HC group, we observed a significant increase in serum TC, LDL-C, VLDL-C, TG, sCD40, and IL-6 levels and platelet activation markers compared with levels in the control group. However, t-resveratrol administration to the HC group (HCR group) attenuated the increase in lipids, sCD40, and IL-6 and down-regulated platelet P-selectin, CD40, and CD40L expressions. A positive correlation was found for serum lipids and all the platelet activation markers. Our study showed that the CD40-CD40L dyad is up-regulated in the presence of hypercholesterolemia and that t-resveratrol administration down-regulated the increase. Key words: resveratrol, hypercholesterolemia, platelet activation, P-selectin, CD40, CD40L. Cette etude se propose de verifier si le irans-resveratrol (t-resveratrol), un constituant du vin rouge reconnu pour ses effets cardioprotecteurs, peut influer sur le ligand de CD40 (CD40L) et sur ses recepteurs CD40 dans les plaquettes de rats hypercholesterolemiques. Soixante rats Wistar sont repartis dans 5 groupes : controle (C), ethanol (E), t- resveratrol (R), hypercholesterolemie (HC) et hypercholesterolemie avec t-resveratrol (HCR). On installe les rats des groupes C, E et R sur une diete normale durant 80 jours. Durant les 20 dernieres journee