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Abstract: FR-OR29

Effects of NOS3 and Nitric Oxide Releasing Bionanomatrix Gel on Reducing Intimal Hyperplasia and Vascular Remodeling

Session Information

Category: Dialysis

  • 703 Dialysis: Vascular Access

Authors

  • Somarathna, Maheshika Srimali, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Isayeva Waldrop, Tatyana, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Hwang, Patrick, Endomimetics, LLC, Birmingham, AL, Birmingham, Alabama, United States
  • Northrup, Hannah M., University of Utah Health, Salt Lake City, Utah, United States
  • Falzon, Isabelle Dorothy, University of Utah Health, Salt Lake City, Utah, United States
  • Shiu, Yan-Ting Elizabeth, University of Utah Health, Salt Lake City, Utah, United States
  • Jun, Ho-Wook, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Lee, Timmy C., The University of Alabama at Birmingham, Birmingham, Alabama, United States
Background

An arteriovenous fistula (AVF) is the preferred type of vascular access in hemodialysis patients. However, nearly 60% of AVFs created develop AVF maturation failure due to venous intimal hyperplasia (IH) formation and poor vascular remodeling (VR). We hypothesize that the endothelial nitric oxide synthase (NOS3) system is critical for reduction of IH and outward VR and local nitric oxide (NO) delivery at the time of AVF creation can enhance AVF maturation

Methods

To explore the role of NOS3, AVFs were created in NOS3 -/-, NOS3 +/+ and NOS3 overexpression mice. To investigate the efficacy of NO gel, rat femoral AVFs were created and immediately after, therapy was applied on the anastomosis. Animals were sacrificed at 7 days following AVF creation to evaluate histomorphological changes. MRI based computational fluid dynamic simulations were performed to investigate hemodynamic changes

Results

As compared to the controls, overexpression of NOS3 can significantly 1) reduce venous IH 2) promote hemodynamic adaptation and VR by increasing venous cross-sectional area, reducing wall shear stress and vorticity through elevating cGMP levels. NO gel therapy had similar significant effects, including reduction of IH (P <0.0091, 70%). In addition, the NO treated group showed significant reduction in intimal α-SMA, vimentin, desmin and MCP-1 levels. Furthermore, slow degradation of NO-releasing gel resulted in prolonged release of NO during the AVF maturation process

Conclusion

NOS3-NO-cGMP system is a critical regulator of AVF remodeling. Thus NO-releasing gel has great potential to promote clinically successful AVF maturation

Funding

  • NIDDK Support