Effect of atorvastatin on inflammation through the Crim1 pathway in HUVECS

LIU Xue-hui; WU Li-mei; LIU Da-bin; CHEN Qi-jun; KUANG Lu; LIU Hua-sen; WU Shao-guo

doi:10.13820/j.cnki.gdyx.20241942

Abstract：Objective To investigate the regulatory effects of atorvastatin calcium salt trihydrate(ATV)on cycteine-rich motor neuron 1(Crim1)and inflammatory cytokines in human umbilical vein endothelial cells(HU-VECs),and to provide a preliminary study on the effect of Crim1 on atherosclerosis.Methods Real-time quantitative PCR(qRT-PCR)and Western blot analysis were used to explore the effects of ATV on inflammation in HUVECs.Im-munohistochemistry was employed to analyze Crim1 expression in atherosclerotic plaques.Results Immunohistochemical analysis revealed that compared with normal endothelial tissue,the mRNA and protein levels of Crim1 were significantly upregulated in atherosclerotic plaques(P＜0.001).Bioinformatics analysis showed a co-expression relationship between Criml and interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and nuclear factor-κB(NF-κB).Experi-mental results demonstrated that ATV significantly downregulated Crim1 mRNA and protein levels,and reduced the ex-pression of IL-6,TNF-α,and NF-κB,thereby inhibiting the inflammatory response.Furthermore,siRNA-mediated silencing of Crim1 significantly inhibited the expression of IL-6,TNF-α,and NF-κB.Overexpression of Crim1 using the recombinant plasmid pcDNA led to a significant increase in IL-6,TNF-α,and NF-κB expression.Group inter-vention experiments showed that ATV attenuated the inflammatory effects induced by Crim1.Conclusion The results in-dicate that ATV mediates the suppression of endothelial cell inflammation via Crim1,providing new insights into the non-lipid-lowering functions of ATV.This study also offers a novel direction for the prevention and treatment of atherosclerosis.