Abstract: TH-PO749

Altered Molecular Profiles in Hemodynamically Vulnerable Segments of Arteriovenous Fistulae (AVF) in a Uremic Pig Model

Session Information

Category: Dialysis

  • 603 Hemodialysis: Vascular Access

Authors

  • Janda, Jaroslav, University of Arizona, Tucson, Arizona, United States
  • Campos, Begoña, University of Cincinnati, Cincinnati, Ohio, United States
  • Jarrouj, Aous, Banner-University of Arizona, Tucson, Arizona, United States
  • Brosius, Frank C., University of Arizona, Tucson, Arizona, United States
  • Kohler, Lindsay N, University of Arizona, Tucson, Arizona, United States
  • Roy-Chaudhury, Prabir, University of Arizona, Tucson, Arizona, United States
  • Celdran-Bonafonte, Diego, University of Arizona / BIO 5 Institute, Tucson, Arizona, United States
Background

Arteriovenous fistulae (AVF) are the preferred vascular access for hemodialysis patients but are subject to stenosis, disrupted flow and failure. The uremic pig serves as a useful model for studying the pathogenesis of AVF dysfunction in humans. Previously, we reported properties of vascular structure and flow in pig AVF that mimicked changes in human AVF. In the current project, we determine whether known differences in AVF hemodynamics between the inner and outer curves of the venous segment of an AVF and between the anastomotic and more proximal segments, were associated with altered gene expression for 8 candidate genes in adjacent AVF segments.

Methods

Renal insufficiency in 4 Yorkshire pigs was surgically induced by 5/6 nephrectomy, and 2 weeks later bilateral AVFs were created between femoral arteries and veins. The inner and outer curves of each AVF were harvested 6 wk later. Four sequential samples from the anastomosis to the more proximal venous segment were collected for each AVF. cDNA was generated from total RNA from these individual segments. Quantitative real time-PCR reactions were performed for ICAM, VCAM, NOS3, NOX4, KLF2, CCL2, MMP2, and MMP9.

Results

MMP9 levels (average of all four venous segments) were consistently and significantly higher in the outer curve of the AVF than the inner curve (p < 0.05). ICAM and VCAM mRNA levels also showed similar trends. eNOS levels trended towards being lower at the anastomosis (both inner and outer curves) as compared to the most proximal venous segment.

Conclusion

Our findings suggest that differences in fluid hemodynamics especially wall shear stress (we have previously demonstrated differences in wall shear stress [WSS] between the inner and outer curves of an AVF, and also between the anastomosis and more proximal segment), could be important determinants of the molecular profile (and subsequent stenosis or lack thereof) in AVFs . Future studies will aim to assess whether manipulation of both upstream WSS and downstream molecular biology (as identified in this work) could reduce AVF stenosis in our uremic pig model.

Funding

  • NIDDK Support