Increase of wall shear stress caused by arteriovenous fistula reduces neointimal hyperplasia after stent implantation in healthy arteries

Abstract

Background and objectives

Wall shear stress plays a critical role in neointimal hyperplasia after stent implantation. It has been found that there is an inverse relation between wall shear stress and neointimal hyperplasia. This study hypothesized that the increase of arterial wall shear stress caused by arteriovenous fistula could reduce neointimal hyperplasia after stents implantation.

Methods and results

Thirty-six male rabbits were randomly divided into three groups: STENT, rabbits received stent implantation into right common carotid artery; STENT/arteriovenous fistula, rabbits received stent implantation into right common carotid artery and carotid-jugular arteriovenous fistula; Control, rabbits received no treatment. After 21 days, stented common carotid artery specimens were harvested for histological staining and protein expression analysis. In STENT group, wall shear stress maintained at a low level from 43.2 to 48.9% of baseline. In STENT/arteriovenous fistula group, wall shear stress gradually increased to 86% over baseline. There was a more significant neointimal hyperplasia in group STENT compared with the STENT/arteriovenous fistula group (neointima area: 0.87 mm² versus 0.19 mm²; neointima-to-media area ratio: 1.13 versus 0.18). Western blot analysis demonstrated that the protein level of endothelial nitric oxide synthase in STENT group was significantly lower than that in STENT/arteriovenous fistula group, but the protein levels of proliferating cell nuclear antigen, vascular cell adhesion molecule 1, phospho-p38 mitogen-activated protein kinase (Pp38), and phospho-c-Jun N-terminal kinase in STENT group were significantly higher than that in the STENT group.

Conclusion

High wall shear stress caused by arteriovenous fistula as associated with the induction in neointimal hyperplasia after stent implantation. The underlying mechanisms may be related to modulating the expression and activation of endothelial nitric oxide synthase, vascular cell adhesion molecule 1, p38, and c-Jun N-terminal kinase.