Involvement of the toll-like receptors-2/nuclear factor-kappa B signaling pathway in atherosclerosis induced by high-fat diet and zymosan A in C57BL/6 mice

Abstract

OBJECTIVE: Accumulated evidence reported a link between the immune system, microbial infection, and the development of atherosclerosis. Excess intake of high-fat diet (HFD) increases blood lipid levels and induces inflammatory pathways whereas zymosan A (Zym), a microbial component, mediates inflammatory response through the stimulation of specific ligand of toll-like receptors (TLRs) of the immune system. The current research work was aimed to evaluate the mechanism behind atherosclerosis mediated by HFD and Zym in C57BL/6 mice. MATERIALS AND METHODS: The mice were orally fed with HFD for 30 days and Zym (80 mg/kg, single intraperitoneal injection on day 8 th ). On the 31 st day, blood was withdrawn from overnight fasted mice by tail vein puncture and estimated for serum lipids and tumor necrosis factor-alpha (TNF-α). Animals were sacrificed, and cardiac, liver, and aortic tissues were isolated for the estimation of cardiac TLR-2, nuclear factor-kappa B (NF-ƙB); hepatic low-density lipoprotein receptors (LDLR); and base of aorta analyzed for histopathology. RESULTS: It was found that HFD and Zym administration increased arterial inflammation directly through modulation of the TLR-2/NF-ƙB pathway, thereby upregulate serum TNF-α, cardiac TLR-2, and NF-ƙB levels. Further, HFD and Zym treatment significantly increased serum lipid levels and marked decrease in LDLR protein expression in the liver when compared to normal control mice. Histopathological analysis showed the formation of atherosclerotic plaque. CONCLUSION: The study is first, to our current knowledge, to demonstrate the involvement of the TLR-2/NF-ƙB signaling pathway in atherosclerosis induced by HFD and Zym in C57BL/6 mice, resulting in increased degradation of LDLR protein, thereby, increasing the serum lipid levels.