The arteriovenous fistula has been used for more than 50 years to provide vascular access for patients undergoing hemodialysis. More than 1.5 million patients worldwide have end stage renal disease and this population will continue to grow. The arteriovenous fistula is the preferred vascular access for patients, but its patency rate at 1 year is only 60%. The majority of arteriovenous fistulas fail because of intimal hyperplasia. In recent years, there have been many studies investigating the molecular mechanisms responsible for intimal hyperplasia and subsequent thrombosis. These studies have identified common pathways including inflammation, uremia, hypoxia, sheer stress, and increased thrombogenicity. These cellular mechanisms lead to increased proliferation, migration, and eventually stenosis. These pathways work synergistically through shared molecular messengers. In this review, we will examine the literature concerning the molecular basis of hemodialysis vascular access malfunction.

Vascular lesions have a varied appearance and can commonly occur in the head and neck. A majority of these lesions are cutaneous and congenital; however, some may be acquired and malignant. The presentation and clinical history of patients presenting with head and neck lesions can be used to guide further imaging, which can provide important diagnostic and therapeutic considerations. This review discusses the revised International Society for the Study of Vascular Anomalies (ISSVA) classification system for vascular tumors and malformations, as well as explores the most common vascular anomalies including their clinical presentations and imaging findings.

Arteriovenous fistulas (AVFs) used for hemodialysis fail because of venous neointimal hyperplasia (VNH). There are 1,500,000 patients that have end stage renal disease worldwide and the majority requires hemodialysis. In the present study, the role of the intermediate early response gene X-1 (IEX-1), also known as IER-3 in the pathogenesis of VNH was evaluated. In human samples removed from failed AVF, there was a significant increase in IEX-1 expression localized to the adventitia. In Iex-1 −/− mice and wild type (WT) controls, chronic kidney disease was induced and an AVF placed 28 days later by connecting the carotid artery to jugular vein. The outflow vein was removed three days following the creation of the AVF and gene expression analysis demonstrated a significant decrease in vascular endothelial growth factor-A (Vegf-A) and monocyte chemoattractant protein-1 (Mcp-1) gene expression in Iex-1 −/− mice when compared to WT mice (P<0.05). At 28 days after AVF placement, histomorphometric and immune-histochemical analyses of the outflow vein demonstrated a significant decrease in neointimal hyperplasia with an increase in average lumen vessel area associated with a decrease in fibroblast, myofibroblast, and Ly6C staining. There was a decrease in proliferation (Ki-67) and an increase in the TUNEL staining in Iex-1 KO mice compared to WT. In addition, there was a decrease in Vegf-A, Mcp-1, and matrix metalloproteiniase-9 (Mmp-9) staining. Iex-1 expression was reduced in vivo and in vitro using nanoparticles coated with calcitriol, an inhibitor of Iex-1 that demonstrated that Iex-1 reduction results in decrease in Vegf-A. In aggregate, these results indicate that the absence of IEX-1 gene results in reduced VNH accompanied with a decrease in proliferation, reduced fibroblast, myofibroblast, and Ly6C staining accompanied with increased apoptosis mediated through a reduction in Vegf-A/Mcp-1 axis and Mmp-9. Adventitial delivery of nanoparticles coated with calcitriol reduced Iex-1 and VNH.

Purpose The purpose of this study was to determine if adventitial transplantation of human adipose derived mesenchymal stem cell (MSC) to the outflow vein of B6.Cg-Foxn1nu/J mice with AVF at the time of creation would reduce monocyte chemoattractant protein-1 (Mcp-1) gene expression and venous neointimal hyperplasia (VNH). The second aim was to track transplanted 89 zirconium (89Zr) labeled MSCs serially by positron emission tomography (PET) imaging for 21 days. Materials and Methods All animal experiments were performed according to protocols approved by our institutional animal care and use committee. We used fifty B6.Cg-Foxn1nu/J mice to accomplish the aims outlined in the current paper. 2.5 × 105 MSC cells were stably labeled with green fluorescent protein (GFP) and injected into the adventitia of the outflow vein at the time of AVF creation in MSC group. Eleven mice died after AVF placement. Animals were sacrificed at day 7 following AVF placement for real time polymerase chain reaction (qRT-PCR, n=6 for MSC and control groups) and histomorphometric analyses (n=6, n=6 for MSC and control groups) and at day 21 for histomorphometric analysis only (n=6 for MSC and control groups). In a separate group of experiments (n=3), transplanted 89zirconium (89Zr) labeled MSCs animals were serially imaged by PET imaging for 3 weeks. Multiple comparisons were performed with two-way ANOVA followed by Student t-test with post hoc Bonferroni’s correction. Results We observed that in MSC transplanted vessels when compared to control vessels, there was a significant decrease in the Mcp-1 gene expression (day 7: average reduction: 62%, P=0.029) with a significant increase in the average lumen vessel area (day 7: average increase: 176%, P=0.013; day 21: average increase: 415%, P=0.011); Moreover, this was accompanied with a significant decrease in Ki-67 index (proliferation, day 7: average reduction: 81%, P=0.0003; day 21: average reduction: 60%, P=0.016 Prolonged retention of MSCs at the adventitia was evidenced by serial PET images of 89Zr-labeled cells. Conclusion These results indicate that adventitial transplantation of MSC decreases Mcp-1 gene expression accompanied with a reduction in VNH.