Abstract
Objective: Understanding the molecular mechanisms of vascular remodeling is critical to improving outcomes following revascularization procedures. While extensive animal data exists, correlative data on the mechanisms and kinetics of vascular healing in humans are lacking. Creation of brachio-basilic arteriovenous fistulas (AVF), often completed in 2 stages, offers an opportunity to examine the same vessel at 2 distinct time points. We hypothesized that immune and developmental related pathways are involved in AVF maturation. Methods: Human basilic vein samples were obtained at the time of AVF creation as baseline. Second samples were taken at basilic vein transposition after exposure to arterial hemodynamic forces. These paired samples were analyzed for differential gene expression using whole genome microarray. Structural staining and confirmatory qPCR were performed in selected genes. Results: Paired vein samples were collected from 3 patients. All subjects had successful AVF maturation. An average of 3 months transpired between collection of the first and second samples. Overall, 700 genes were significantly down-regulated and 732 genes were significantly up-regulated. Gene ontogeny analysis revealed no difference in the genes regulating developmental re-activation pathways or angiogenesis. However, inflammatory and fibrosis genes were still significantly up-regulated 3 months following AVF creation (p <<.05). Structural stains confirmed an increase in lumen and total vessel area and deposition of elastin and collagen with significant intimal hyperplasia between baseline and 3 month samples. Additionally, qPCR showed a 9.7 fold increase in IL-6 and a 10.4 fold increase in e-selectin at 3 months. Conclusions: Inflammatory and fibrosis gene pathways remain activated in mature fistulas despite stabilization of geometric remodeling. Further study is warranted to characterize these pathways and determine their significance in AVF patency.
Published Version
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