The Role Of KLF2?VEGF-A And VCAM-1 In The Pathogenesis Of Autogenous Arteriovenous Fistula Stenosis

Objective:Autologous arteriovenous fistula is the preferred vascular pathway for hemodialysis in patients with end-stage renal disease.Stenosis is known to be AVF most common complication.AVF stenosis is mainly caused by intimal hyperplasia.Histological characteristics of intimal hyperplasia are that a large number of contractible smooth muscle cells,fibroblasts,fibroblasts and macrophages cause venous lumen stenosis,inflammation is one of the biological mechanisms of intimal hyperplasia.Vascular endothelial growth factor-A(VEGF-A)is a highly specific pro-vascular endothelial cell growth factor that promotes endothelial cells and smooth muscle cell proliferation and migration,while promoting monocyte,macrophage aggregation,and plays an important role in AVF intimal hyperplasia.VEGF-A also acts as proinflammatory cytokines and induce the expression of many molecules associated with regulating angiogenesis.Kruppel Like Factor(KLF),the transcription factors of the family are a subclass of the transcription regulators of the zinc finger family involved in the regulation of cell growth and differentiation.A member of this family is significantly expressed KLF2 endothelial cells and is a key regulator of endothelial function.This experiment investigated the changes in the expression levels of KLF2?VEGF-A and VCAM-1 in human autogenous arteriovenous fistula stenosis tissue,to explore the relationship between the above factors and AVF intimal hyperplasia,and the relationship between the expression of the three factors,and then clarified the mechanism of KLF2 mediated inflammatory response in the stenosis of internal fistula,to provide therapeutic targets for early intervention.Methods:Collectting intraoperative abandoned veins from the patients with AVF angioplasty and reconstruction of AVF in The Third Hospital of Hebei Medical University from october 2018 to october 2019 for maintenance hemodialysis treatment.The venous tissue of the stenosis portion of the patient undergoing AVF reconstruction was retained as experimental group(n =10).The intraoperative ligation of the veins in the patients with the first AVF angioplasty was set as a control group(n =10).Observing the degree of venous intimal hyperplasia by hematoxylin-eosin staining(HE),the expression levels of KLF2,VEGF-A and VCAM-1 were detected by immunohistochemical staining in each group,and the relationship between the expression levels of these factors and venous intimal hyperplasia was analyzed.The experimental data were statistically analyzed by SPSS21.0 statistical software,the results were expressed as mean ± standard deviation,and P <0.05 represented the difference was statistically significant.Results:There was no significant statistical difference in age and sex between the two groups(P>0.05).There was no difference in primary disease between the two groups.1.HE staining: Under light microscope,the intima and media tissue of the experimental group were thickened to varying degrees,and the intima thickening was more obvious than that of the middle membrane.The proliferating intima protruded to the official lumen and even resulted in lumen occlusion.The intimal media thickness ratio was 4.79±2.28 in the experimental group and 0.18±0.08 in the control group.The difference between the experimental group and the control group was statistically significant(t=6.383,P=0.000).2.Immunohistochemical staining 2.1 KLF2:The expression in the experimental group(0.00073±0.00090)was smaller than that in the control group(0.00234±0.00081),and the difference was statistically significant(t=-4.182,P=0.001).2.2 VEGF-A:The expression was greater in the experimental group(0.00278±0.00058)than in the control group(0.00278±0.00058),and the difference was statistically significant(t=7.293,P=0.000).2.3 VCAM-1:The expression was greater in the experimental group(0.00196±0.00139)than in the control group(0.00051±0.00025),and the difference was statistically significant(t=3.231,P=0.010).3.Correlation analysis:There was a negative correlation between VEGF-A and KLF2 expression levels(r=-0.675,P=0.032),and a positive correlation between VCAM-1 and VEGF-A expression levels(r=0.849,P=0.002).Conclusion:1.The expression of VEGF-A and VCAM-1 in AVF narrow venous tissue was significantly increased,and VEGF-A could induce the expression of VCAM-1.2.AVF expression of KLF2 in the narrow venous tissue is downregulated,which in turn promotes VEGF-A mediated intimal hyperplasia,indicating that the occurrence of AVF stenosis may be related to the decrease of KLF2 expression level.