Abstract
Background: Arteriovenous fistula (AVF) stenosis remains an important cause of AVF maturation failure, for which there are currently no effective therapies. We examined the pattern and phenotype of cellular proliferation at different timepoints in a mouse model characterized by a peri-anastomotic AVF stenosis. Methods: Standard immunohistochemical analyses for cellular proliferation and macrophage infiltration were performed at 2, 7 and 14 d on our validated mouse model of AVF stenosis to study the temporal profile, geographical location and cellular phenotype of proliferating and infiltrating cells in this model. Results: Adventitial proliferation and macrophage infiltration (into the adventitia) began at 2 d, peaked at 7 d and then declined over time. Surprisingly, there was minimal macrophage infiltration or proliferation in the neointimal region at either 7 or 14 d, although endothelial cell proliferation increased rapidly between 2 d and 7 d, and peaked at 14 d. Conclusions: Early and rapid macrophage infiltration and cellular proliferation within the adventitia could play an important role in the downstream pathways of both neointimal hyperplasia and inward or outward remodelling.
Highlights
Arteriovenous fistula (AVF) nonmaturation is currently a critical clinical problem responsible for significant morbidity, mortality and economic cost [1,2,3]
We have previously demonstrated that AVF nonmaturation is characterized by tight perianastomotic venous narrowing [4], probably due to the combination of a lack of outward remodelling and the presence of aggressive venous neointimal hyperplasia [2,5]
AVF stenosis primarily occurs in the peri-anastomotic regions of both radio-cephalic and brachiocephalic AVFs, and in the cephalic arch region
Summary
Arteriovenous fistula (AVF) nonmaturation (defined as an arteriovenous fistula that does not develop an adequate blood flow or lumen diameter to support haemodialysis) is currently a critical clinical problem responsible for significant morbidity, mortality and economic cost [1,2,3]. AVF stenosis primarily occurs in the peri-anastomotic regions of both radio-cephalic and brachiocephalic AVFs, and in the cephalic arch region (downstream of brachiocephalic AVFs) [6] Despite the magnitude of the clinical problem, there are currently no effective therapies for AVF nonmaturation. This is likely due to insufficient knowledge about the interactions between haemodynamic injury and the vascular response to injury, especially oxidative stress (likely magnified by the presence of uraemia) [2,5]. Conclusions: Early and rapid macrophage infiltration and cellular proliferation within the adventitia could play an important role in the downstream pathways of both neointimal hyperplasia and inward or outward remodelling
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