Abstract:Percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF. In human stenotic samples from AVFs, we demonstrated increased gene expression of Ier3. We hypothesiz… Show more
“…In support of the importance of the adventitia in vascular stenoses, we note studies where adventitial injury and activation is associated with vascular stenosis [24][25][26] and also studies by Misra et al in a mouse AVF stenosis model where adventitial therapy with a blocker of CX3CR1 [27] reduced peri-anastomotic stenosis and adventitial delivery of Vitamin D, both post angioplasty in a mouse model [28], and also reduced venous stenosis.…”
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.
“…In support of the importance of the adventitia in vascular stenoses, we note studies where adventitial injury and activation is associated with vascular stenosis [24][25][26] and also studies by Misra et al in a mouse AVF stenosis model where adventitial therapy with a blocker of CX3CR1 [27] reduced peri-anastomotic stenosis and adventitial delivery of Vitamin D, both post angioplasty in a mouse model [28], and also reduced venous stenosis.…”
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.
“…A recent study performed in a pig AVF model with chronic kidney disease showed that adventitial delivery of poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulated with 1α,25(OH) 2 D3 (1,25 NP), compared to vehicle controls, delivered to the adventitia of the outflow vein after AVF creation reduced venous stenosis formation (Figure 5) by decreasing inflammation and fibrosis 46 . Another study using a mouse model showed that PLGA nanoparticles encapsulated with 1α,25(OH) 2 D3 and delivered to the adventitia of the outflow vein after angioplasty decreased venous neointimal hyperplasia and restenosis by decreasing inflammation and apoptosis pathways 47 . Other studies have demonstrated that using microparticles coated with simvastatin to the adventitia of the outflow vein of experimental animals can reduce venous stenosis formation 48 .…”
The hemodialysis population continues to grow. Although procedures for dialysis have existed for over 60 years, significant challenges with vascular access to support hemodialysis persist. Failure of arteriovenous fistulas (AVFs) to mature, loss of AVF and graft patency, thrombosis and infection hinder long-term access and add extra health care costs as well as patient morbidity. There have been numerous innovations over the last decade aimed at addressing the issues. Herein, we review the literature and summarize the recent evolution of drug delivery, graft development, minimally invasive AVF creation, and stem cell therapy for hemodialysis access.
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