Early Adventitial Activation and Proliferation in a Mouse Model of Arteriovenous Stenosis: Opportunities for Intervention

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.

Molecular Insights and Novel Approaches toward Individualized Arteriovenous Fistula Care

“…Interestingly, a recent study showed that blockade of CX 3 CR1 signaling leads to reduced venous stenosis and improved AVF patency using a humanized mouse model [31]. In another study using a mouse stenosis model [32], macrophages were found to infiltrate into the outer layer at a fast rate and slowly decline over time and only minimal macrophage infiltration happened in the neointimal later in the AVF stenosis. The findings from these two animal studies on AVF stenosis suggest that after AVF forms, early intervention by inhibiting CX 3 CR1 signaling may prevent stenosis and improve patency.…”

Molecular Mechanisms of Hemostasis, Thrombosis and Thrombo-Inflammation

“…These interactions may also affect proliferation processes in the vessel wall. Chan et al [ 21 ] showed in a mouse model of arteriovenous fistula stenosis that both macrophage infiltration and cellular proliferation in the adventitia occur rapidly in the early stages of vascular remodeling. These results may be important for intervention strategies to prevent arteriovenous fistula maturation failure.…”