Modulatory role of atorvastatin against high-fat diet and zymosan-induced activation of TLR۲/NF-ƙB signaling pathway in C۵۷BL/۶ mice

Objective(s): Accumulated evidence provides a strong connection between the immune system and vascular inflammation. The innate immune system’s main sensors are toll-like receptors (TLRs). Zymosan (Zym), a fungal product, induces an inflammatory response via activating TLR۲ of the immune system. Atorvastatin, a potent statin, possesses pleiotropic effects including immunomodulatory, lipid-lowering, and anti-inflammatory. Therefore, the current study aimed to evaluate the protective role of atorvastatin against a high-fat diet (HFD) and Zym-induced vascular inflammation in C۵۷BL/۶ mice via modulation of TLR۲/NF-ƙB signaling pathway.Materials and Methods: In silico study was conducted to confirm the binding affinity of atorvastatin against TLR۲. Under in vivo study, mice were divided into four groups: Normal control: normal standard chow-diet fed for ۳۰ days + Zym vehicle (sterile PBS, ۵ mg/ml on ۸th day); HFD (۳۰ days) + Zym (۸۰ mg/kg, IP, on ۸th day); HFD/Zym + atorvastatin vehicle (۰.۵% CMC, p.o., from ۱۰th to ۳۰th day); HFD/Zym + atorvastatin (۳.۶ mg/kg, p.o., from ۱۰th to ۳۰th day).Results: Atorvastatin treatment along with HFD and Zym inhibited vascular inflammation by suppressing the levels of aortic TLR۲, cardiac NF-ƙB and decrease in serum TNF-α and IL-۶. Further, there was an increase in hepatic LDLR levels, resulting in a decrease in serum LDL-C and an increase in HDL-C levels. Histopathological examination of the aorta showed a reduction in plaque accumulation with the atorvastatin-treated group as compared with HFD and Zym-treated group.Conclusion: Atorvastatin attenuates vascular inflammation mediated by HFD and Zym through suppression of TLR۲, NF-ƙB, TNF-α, IL-۶, and upregulation of LDLR levels.

Keywords:

Atorvastatin High , fat diet Inflammation Low , density lipoprotein , receptor Nuclear factor , kappa B Toll , like receptor Zymosan