Abstract 225: Parallel and Divergent Patterns of Gene Expression in Human Arteriovenous Fistula Maturation and Stenosis

Abstract

Background: The biologic mechanisms that differentiate successful arteriovenous fistula (AVF) maturation from stenosis are not well understood. The brachiobasilic transposition offers an opportunity for studying the vascular remodeling process. This procedure is a two stage process: first to create a brachiobasilic AVF and second, to transpose the AVF near the skin in a delayed fashion, allowing the opportunity to harvest naïve vein, mature and stenotic AVF tissue. Identifying the molecular differences with regards to success (maturation) or failure (stenosis) are vital both for dialysis access care and as a model of vein remodeling on exposure to arterial flow. We hypothesize that basilic vein transposition (BVT) can be utilized as a unique means with which to study the biologic factors that affect stenosis and maturation. Methods/Results: Vein tissue was obtained at the time of initial access creation as naïve segments and again at the time of basilic vein transposition (following venous “arterialization”), resulting in a cohort of patient-matched naïve, mature, and stenotic segments. Time between procedures ranged from 3-8 months, with a mean of 5. Vein segments were scored at time of collection as mature or stenotic, and confirmed by histology. Real-time PCR was performed on extracted RNA using a panel of genes implicated in the process and regulation of both successful and “unsuccessful” vascular wall remodeling. Heme oxygenase-1, matrix metalloproteinase-9 (MMP9) and osteopontin (SPP1) are significantly upregulated in both mature and stenotic vein segments (vs. naïve); MMP9 and SPP1 were also significantly upregulated in mature vs. stenotic tissue. SPP1 was exclusively expressed in the medial region of mature and stenotic AVF. Stenotic samples demonstrated a significant increase in the expression of tissue inhibitor of metalloproteinase-1 (MMP-1) and endothelin-1 (EDN-1) versus both naïve and mature samples. Conclusion: The BVT offers a unique opportunity to identify potential mechanisms involved in AVF maturation and stenosis. There appears to be overlap in gene expression profiles for both mature and stenotic samples, however MMP-1 and EDN-1 appear to be significantly increased in venous stenosis.