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Abstract: FR-PO464

Nitric Oxide-Releasing Nanomatrix Gel Inhibits Venous Intimal Hyperplasia and Improves Vascular Remodeling in Porcine Arteriovenous Fistula (AVF)

Session Information

  • Dialysis: Vascular Access
    November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

  • 803 Dialysis: Vascular Access

Authors

  • Nguyen, Nguyen TN., The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Ingle, Kevin Andrew, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Isayeva Waldrop, Tatyana, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Lose, Bailey Gene, The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Collie, Paul C., The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Gard, William A., The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
  • Hwang, Patrick, Endomimetics, LLC, Birmingham, Alabama, United States
  • Jun, Ho-Wook, The University of Alabama at Birmingham School of Engineering, Birmingham, Alabama, United States
  • Northrup, Hannah M., University of Utah Health, Salt Lake City, Utah, United States
  • Shiu, Yan-Ting Elizabeth, University of Utah Health, Salt Lake City, Utah, United States
  • Lee, Timmy C., The University of Alabama at Birmingham Heersink School of Medicine, Birmingham, Alabama, United States
Background

Arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis, but a large proportion fails to mature due to venous intimal hyperplasia (IH) formation and impaired outward remodeling. End-stage kidney disease has been linked to endothelial dysfunction characterized by reduced nitric oxide(NO) in the blood vessel. NO delivery during AVF creation may improve AVF maturation. Our study tested an NO nanomatrix gel applied perivascularly during AVF creation in a porcine AVF model.

Methods

AVFs were created in Yorkshire pigs by anastomosing the jugular vein to the carotid artery, treated with NO-releasing nanomatrix or control gel at the anastomosis, and sacrificed at day 35. Immunohistochemistry, histomorphology and hemodynamic changes were evaluated to assess the efficacy of NO gel in reducing intimal hyperplasia and promoting outward remodeling.

Results

NO gel-treated group vs control gel demonstrated significantly reduced IH(p<0.0001) and type I collagen(p<0.05). The patency of open lumen within AVF region was significantly higher in NO gel, along with increased blood flow and AVF diameter(p<0.05). NO gel reduced intimal α-SMA, Vimentin, Desmin, CD68 and CD14 expression(p<0.05).

Conclusion

AVFs applied with an NO-releasing gel reduce intimal hyperplasia and promote outward remodeling, and could serve as a therapy to promote AVF maturation.

Funding

  • NIDDK Support