The Relationship Between Hypoxia Inducible Factor-1α Expression And Novoendotheliasis After Autogenous Vein Grafting

As the wide use of vein grofts in treating coronary artery disease and peripheral artery chemic disease , the stenosis of transplanted vein caused by intimal hyperplasia has become the main factor affecting the long term patency . But in the early period after the operation ( 30 days postoperation ) , the blocking ratio of the veins is 5 - 26% ; and in the late stage ( ≥ years postoperation ) , the blocking ratio will up to 40% . That restenosis is mainly caused by intimal hyperplasia (IH) and sclerosis . So restenosis reduce the therapeutic effectiveness seriously . The mechanism of IH is not very clear yet . But it is associated with injury , ischemia , PDGF, hemodynamic change , etc. Therefore, how to inhibit the intimal hyperplasia of transplanted vein has become an important topic of vascular surgery.We have known that the vascular endothelial cell( VEC) plays an important roles in supporting and rebuilding the normal construction of vein. Hypoxia inducible factor - lα( HIF - lα) controls and rejusts the expression of Vascular endothelial growth factor ( VEGF) gene. To elucidate the relationship between level of hypoxia inducible factor - lαexpression and novoendotheliasis after autogenous vein grafting, we can find a new method to prevent restenosis of transplanted vein and provide experimental basis for clinical requirement.MethodWe use wistar rats to establish the model of common jugular vein interplaced to common carotid artery through microsurgery . The vein grafts from 40 experimental animals and normal vein from 20 control animals were studied. 40 Wister rats underwent the right internal jug-ular vein to common jugular artery interposition grafts. The grafted vein was harvested at 7 and 14 days respectively after grafted . The samples are fixed in 10% Neutal formalin or frozen rapidly in liquid nitrogen and reserved - 70^?C. Hypoxia inducible factor-1αand vas-cular endothelial growth factor expression was examined by using Western blotting, respectively. Electron microscope was used to ob-serve the process of vascular novoendotheliasis . Immunohistochemistry was used to observe the expression of HIF-1αand α-actin as local-ized vascular smooth muscle cell .ResultsAt both 7 days and 14 days postoperatively , the expression of HIF ?lαand VEGF index was obviously inhibited in the experimental group than the control groups ( p < 0. 01). Under the electron micro-scope , we also found the change of phenotype of the vascular smooth muscle cells from contraction to excretion were inhibited.The expression of HIF -1αand VEGF at 7 days was higher than that at 14days ( all p < 0. 01). The process of novoendotheliasis at 7 days compared with that at 14 days was strongly observed in the speci-mens. Expression of HIF - 1αwithα - actin was shown by immunos-taining in intimal hyperplasia. There was obviously positive correlec-tion between the expression of HIF - lαand VEGF(r =0.903, p <0. 01).ConclusionsThe present findings indicate that there is an association between HIF - lα and novoendotheliasis and suggest that HIF - lαtplay an im-portant role in the development of IH.