The Expression Of Vasa Vasorum In The Stenotic Lesions Of Arteriovenous Fistula

Objective: The arteriovenous fistula(AVF)has been placed at patients undergoing hemodialysis for more than 50 years.It has proven to be the preferred vascular access for hemodialysis patients because of its lower rates of infection and complications.The stenosis of venous outflow is the major complication and limitation of arteriovenous fistula plasty in hemodialysis patients.The patency of AVF at 1 year is estimated to be only 62% and that constitutes the leading cause of hospitalization for surgical revision.Intimal hyperplasia is the leading cause of the formation of AVF stenosis.The histology of intimal hyperplasia is characterized by an exaggerated accumulation of smooth muscle cells,myofibroblasts and macrophages.This pathological process included inflammation,uremia,hypoxia,sheer stress.Hypoxia has a importent role in the process of intimal hyperplasia.Intimal thickening can increase the distance of nutrients diffuse,with the addition of the increased energy demanding for cell metabolism in intimal hyperplasia.,there is an increased requirement of oxygen and nourishment to meet the needs of cell proliferation in intima.Previous studys have showed the existence of neovascularization in the thickened vessel wall of coronary with atherosclerotic lesion and demonstrated that neovascularization contributed to the pathogenesis of arteriosclerosis.Intimal hyperplasia is the common pathological feature of atherosclerosis and arteriovenous fistula stenosis.This study was carried out to observe the expression of vasa vasorum in stenosed human AVF and try to explain its role in AVF failure.Methods: Samples were divided into three groups.Experimental group were segments removed form 10 occluded or severely narrowed vein segments of primary arteriovenous fistulas.Segments in the control group A were nonstenotic segments removed form the site close to the stenosis.Segments in the control group B were from vein segments of 10 non-stenosed control veins from uremic,pre-dialysis patients.Intimal hyperplasia was identied by HE staining,morphometric analysis was performed with IPP image analysis software.Neovascularization of vasa vasorum was evaluated by microvascular density.Microvessels in the intimal hyperplasia were identified using immunohistochemical techniques.VEGF-A staining was used to observe the expression of VEGF-A in segments.All data was analyzed by statistical analysis software SPSS 23.0 and expressed as mean ± SE(x?s).P<0.05 were required for statistical significance.Results:1.HE stainingA obviously increased neointimal thickness accompanied with inflammatory cell was found in the sections from the experimental group.While no increased neointimal thickness,inflammatory cell infiltration and angiogenesis were observed in the control group B.The neointimal thickness was slightly increased in self control group.Experimental group has a greater mean ratio of intima thickness /media thickness than the other groups(2.683±0.356 vs.0.686±0.059,P<0.01;2.683±0.356 vs.0.123±0.024;P<0.01;0.686±0.059 vs.0.123±0.024,P<0.01).2.vWF stainingvWF staining was observed at high magnification.Positive staining was mainly expressed in the adventitia,and the stained site was located in the cytoplasm.It was performed to detect vasa vasorums in vessel wall.The number of microvessels in the three groups was counted at 400 x high magnification,and the microvessel density(MVD)was calculated.The results showed adventitial MVD in the experimental group was higher than the other groups(15.923±4.924 vs.6.879±1.821,P<0.01;15.923±4.924 vs.4.586±1.611,P<0.01;6.879±1.821 vs.4.586±1.611,P>0.05).3.VEGF-A stainingVEGF-A staining was located in the cytoplasm.There is a strongly positive staining in the sections from experimental group,while weaklypositive staining was obsevered in the two control groups.The analysis revealed that there was a significant difference in VEGF-A protein expression between experimental and two control groups(0.119±0.438 vs.0.049±0.176,P<0.01;0.119±0.438 vs.0.039± 0.011,P<0.01;0.049±0.176 vs.0.039± 0.011,P>0.05).4.Correlation analysisIn the correlation analysis,a strong relationship was observed between adventitial MVD and the neointimal thickness in stenosed AVF.While,there is a strong relationship between expression of VEGF-A and adventitial MVD.Conclusion:1.There is an increased expression of adventitia vasa vasorum in stenosed AVF.2.There is an increased expression of VEGF-A in stenosed AVF and VEGF-A may correlated with the neogenesis of vasa vasorum.3.The hyperplasia of adventitia vasa vasorum may correlated with the stenoses of arteriovenous fistula.