Objective To explore the molecular mechanism of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors to slow atherosclerosis(AS).Methods A total of 45 apolipoprotein E gene knockout(ApoE-/-)mice were selected as the study objects,and they were divided into control group,AS model group and PCSK9 inhibitor intervention group by random number table method,with 15 mice in each group.Mice in control group were fed a normal diet.The AS model group was established by high-fat diet induction,and the PCSK9 inhibitor intervention group was fed high-fat diet and injected with PCSK9 inhibitors.After the end of experiment,plasma of mice was collected to determine the concentration of blood lipids.Aortic roots of mice were sliced and stained with oil red O and hematoxylin-eosin (HE) to observe pathological changes.The expression of VCAM-1 in aortic tissues of mice in each group was detected by immunohistochemical assay.The mRNA content and protein expression of VCAM-1 in thoracic aorta were determined by real-time PCR and Western Blot.The concentrations of plasma tumor necrosis factor-α (TNF-α) and plasminogen activator inhibitor-1(PAI-1) were determined by ELISA.Results After intervention,plasma levels of total cholesterol (TC),triglyceride (TG)and low-density lipoprotein cholesterol (LDL-C)in AS model group were higher than those in control group,the level of high density lipoprotein cholesterol (HDL-C) was lower than that in control group,the differences were statistically significant (P＜0.05).There were no significant differences in plasma levels of TC,TG,LDL-C and HDL-C between PCSK9 inhibitor intervention group and control group(P＞0.05).The plasma levels of TC,TG and LDL-C in PCSK9 inhibitor intervention group were lower than those in AS model group,and HDL-C was higher than that in AS model group,with statistical significances (P＜0.05).The relative area of aortic atherosclerotic plaque in AS model group was larger than that in control group,the relative area of aortic atherosclerotic plaque in PCSK9 inhibitor intervention group was smaller than that in AS model group,the differences were statistically significant (P＜0.05).VCAM-1 protein expression and mRNA levels in AS model group and PCSK9 inhibitor intervention group were higher than those in control group,VCAM-1 protein expression and mRNA levels in PCSK9 inhibitor intervention group were lower than those in AS model group,the differences were statistically significant(P＜0.05).Plasma TNF-α and PAI-1 levels in AS model group were higher than those in control group,Plasma TNF-α and PAI-1 levels in PCSK9 inhibitor intervention group were lower than those in AS model group,the differences were statistically significant(P＜0.05).There were no significant differences in plasma TNF-α and PAI-1 content between PCSK9 inhibitor intervention group and control group (P＞0.05).Conclusion PCSK9 inhibitors can reduce VCAM-1 expression in aortic tissues by decreasing the concentrations of inflammatory cytokines TNF-α and PAI-1,thus delaying the progression of atherosclerosis.