Resveratrol protects against atherosclerosis by downregulating the PI3K/AKT/mTOR signaling pathway in atherosclerosis model mice

Atherosclerosis is a cardiovascular disease, which is characterized by the interaction between carbohydrates, lipids, cells and various other molecules and genetic factors. Previous studies have demonstrated that resveratrol (RV) served protective roles in numerous types of human disease by regulating different signaling pathways. The aim of the present study was to investigate the therapeutic effects of RV and analyze the potential RV-mediated mechanism in umbilical vein endothelial cells (UVECS) in atherosclerosis model mice. Reverse transcription-quantitative PCR, western blotting and immunohistochemistry were used to analyze the therapeutic effects of RV both in vitro and in vivo. The results demonstrated that total cholesterol, triglycerides, low-density lipoprotein cholesterin and high-density lipoprotein cholesterin levels were significantly decreased in the RV group compared with the control group. RV demonstrated significant anti-atherosclerotic activity, which was determined through the atherogenic index, 3-hydroxy-3-methyl-glutaryl-Coa (HMG-CoA) reductase activity and marker enzymes, such as lactate dehydrogenase, creatine phosphokinase, aspartate transaminase, alanine transaminase and alkaline phosphatase. It was also observed that RV treatment significantly decreased the area of the arteriosclerotic lesion in the RV group compared with the control, as well as significantly decreasing the expression levels of matrix metalloproteinase-9 and CD40 ligand (CD40L) in arterial lesion tissue compared with the control group. Serum expression levels of tumor necrosis factor-α and C-reactive protein were also significantly decreased by RV treatment compared with the control group. Furthermore, RV treatment significantly decreased the expression levels of PI3K, AKT and mTOR in UVECS in vitro. In conclusion, these results suggested that the anti-atherosclerotic activity of RV may be due to its modulatory activity over the PI3K/AKT/mTOR signaling pathway. These findings suggested a potential novel treatment option for patients with atherosclerosis.