Effect of proprotein convertase subtilisin/Kexin type 9 inhibitor as a primary preventive treatment on the occurrence and progression of atherosclerotic plaque in rabbits

Lu Huaizhi; Zhao Hui; Wang Yong; Xu Xuesheng

doi:10.3760/j.issn.1673-4777.2024.08.004

Abstract：Objective To investigate the effect of proprotein convertase subtilisin/Kexin type 9 inhibitor as primary preventive treatment on the occurrence and progression of atherosclerotic plaque in rabbits.Methods Thirty healthy male New Zealand white rabbits were selected and randomly divided into control group,model group and evolocumab group,with 10 rabbits in each group.The control group was fed with normal diet.The model group was fed with high-fat diet and the right carotid artery intima was injured.The evolocumab group was given subcuta-neous injection of evolocumab on the basis of the model group.The peripheral blood of rabbits was collected to detect the lipid levels in each group.The pathological sections of blood vessels in each group were compared.Immunohistochemical staining was used to evaluate the expression of CD68,CD147 and matrix metalloproteinase 9 in the plaques.Results After 13 weeks of high-fat diet,the levels of low-density lipoprotein cholesterol,total cholesterol,and triglyceride in the model group and evolocumab group were higher than those before intervention,and were higher than those in the control group.The levels of low-density lipoprotein cholesterol,total cholesterol,and triglyceride in the model group were higher than those in the evolocumab group[(19.1±1.6)mmol/L vs(11.2±1.3)mmol/L,(22.2±2.4)mmol/L vs(13.1±2.7)mmol/L,(5.8±0.9)mmol/L vs(4.7±0.5)mmol/L](all P＜0.05).There was no plaque formation in the control group,while carotid plaque formation was observed in the model group and the evolocumab group.Macrophages and foam cells were abundant in the intima of the plaque in the model group,large lipid core was seen in the plaque,and the fibrous cap was thin,forming a typical vulnerable plaque.Compared with the model group,the evolocumab group showed more intimal hyperplasia,smaller plaque volume and stenosis,and lower expression of CD 147 and matrix metalloproteinase 9.Conclusions The early intervention of evolocumab can effectively control the levels of low-density lipoprotein cholesterol,total cholesterol and triglyceride,significantly reduce the volume of atherosclerotic plaque and the degree of stenosis,reduce the lipid deposition in the plaque,reduce the inflammatory reaction,and make the plaque more stable.It has the significance of primary prevention and treatment in the formation of coronary athero-sclerotic heart disease.