Atorvastatin inhibits inflammation through the cysteine-rich motor neuron 1 (Crim1) pathway in human umbilical vein endothelial cells

Background and AIMS: Inflammation has been recognized to have a role in the process of atherosclerosis. Although evidence indicates that atorvastatin has anti-inflammatory effects besides cholesterol-lowering ability in atherosclerosis, the specific mechanisms of atorvastatin in inflammation requires further discussion. METHODS: Here, we explored the effects and mechanisms of atorvastatin on inflammation in human umbilical vein endothelial cells through quantitative real-time PCR and western blot analyses. In addition, microarray analysis and immunohistochemistry were used to analyze the expression of Crim1 in atherosclerotic plaques. RESULTS: Cysteine-rich motor neuron 1 (Crim1) mRNA was upregulated 36.68 fold (P<0.001), and Crim1 protein was upregulated 3.63 fold (p<0.001), in human atherosclerotic plaques compared with normal intima tissues. Bioinformatics analysis revealed Crim1 co-expression with IL-6, TNF-α and NF-κB. Atorvastatin dramatically downregulated the mRNA and protein levels of Crim1 and inhibited inflammation by decreasing the levels of IL-6, TNF-α and NF-κB. Knockdown of Crim1 significantly inhibited IL-6, TNF-α and NF-κB expression, whereas overexpression of Crim1 upregulated IL-6, TNF-α and NF-κB expression. In addition, the inhibitory effects of atorvastatin on inflammation were markedly offset by overexpression of Crim1. CONCLUSION: These results demonstrated that atorvastatin decreases inflammation via the Crim1 pathway in HUVECs, thus, providing a new prospect for the use of atorvastatin for non-lipid lowering functions, and new directions for the prevention and therapy of atherosclerosis.