Evaluation of Venous Stenosis Angioplasty in a Murine Arteriovenous Fistula Model

Abstract

PurposeTo develop a clinically relevant model of percutaneous transluminal angioplasty (PTA) of venous stenosis in mice with arteriovenous fistula (AVF); to test the hypothesis that there is increased wall shear stress (WSS) after PTA; and to histologically characterize the vessels. Materials and MethodsThirteen C57BL/6J male mice, 6–8 weeks old, underwent partial nephrectomy to create chronic kidney disease. Twenty-eight days later, an AVF was created from the right external jugular vein to the left carotid artery. Fourteen days later, an angioplasty or sham procedure was performed, and the mice were sacrificed 14 days later for histologic evaluation to identify the cells contributing to the vascular remodeling (α-SMA, FSP-1, CD31, and CD68), proliferation (Ki-67), cell death (TUNEL), and hypoxia staining (HIF-1α). Histomorphometric analysis was performed to assess lumen area, neointima+media area, and cellular density. Ultrasound was performed weekly after creation of the AVF. ResultsVenous stenosis occurred 14 days after the creation of an AVF. PTA-treated vessels had significantly higher WSS; average peak systolic velocity, with increased lumen vessel area; and decreased neointima + media area compared to sham controls. There was a significant decrease in the staining of smooth muscle cells, fibroblasts, macrophages, HIF-1α, proliferation, and apoptosis and an increase in CD31-(+) cells. ConclusionsA clinically relevant model of PTA of venous stenosis in mice was created. PTA-treated vessels had increased lumen vessel area and WSS. The alterations in tissue markers of vascular remodeling, tissue hypoxia, proliferation, and cell death may be implications for future design of drug and device development.