Modulatory role of atorvastatin against high-fat diet and zymosan-induced activation of TLR2/NF-κB signaling pathway in C57BL/6 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 TLR2 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 C57BL/6 mice via modulation of TLR2/NF-kappa B signaling pathway. Materials and Methods: In silico study was conducted to confirm the binding affinity of atorvastatin against TLR2. Under in vivo study, mice were divided into four groups: Normal control: normal standard chow-diet fed for 30 days + Zym vehicle (sterile PBS, 5 mg/ml on 8th day); HFD (30 days) + Zym (80 mg/kg, IP, on 8th day); HFD/Zym + atorvastatin vehicle (0.5% CMC, p.o., from 10th to 30th day); HFD/Zym + atorvastatin (3.6 mg/kg, p.o., from 10th to 30th day). Results: Atorvastatin treatment along with HFD and Zym inhibited vascular inflammation by suppressing the levels of aortic TLR2, cardiac NF-kappa B and decrease in serum TNF-alpha and IL-6. 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 TLR2, NF-kappa B, TNF-alpha, IL-6, and upregulation of LDLR levels.