Abstract: FR-PO978

The Role of Endothelial Nitric Oxide Synthase Expression in Arteriovenous Fistula Remodeling and Hemodynamic Adaptation

Session Information

Category: Bioengineering and Informatics

  • 101 Bioengineering and Informatics

Authors

  • Lee, Timmy C., University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Pike, Daniel, University of Utah, SALT LAKE CITY, Utah, United States
  • Isayeva Waldrop, Tatyana, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Guo, Lingling, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Somarathna, Maheshika Srimali, University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Shiu, Yan-Ting, University of Utah, SALT LAKE CITY, Utah, United States
Background

Endothelial nitric oxide synthase (NOS3), via its role of producing nitric oxide (NO), plays an important role in arteriovenous fistula (AVF) maturation following AVF creation. NOS3 dysfunction may play an important role in AVF development.

Methods

Carotid (side)-jugular (end) AVFs were created in NOS3-/- (knockout), NOS3+/+ (wildtype), and NOS3 overexpression (OE) mice on C57/BL6 background. Serial AVF lumen and hemodynamic changes were characterized using non-contrast MRI-imaging and computation fluid dynamic imaging (Fig. 1). Mice were sacrificed at 21 days for histologic and biochemical studies.

Results

At day 21, NOS3 OE AVFs have large venous lumen at and near the anastomosis, smooth velocity streamlines, low vorticity, as well as relatively uniform and low wall shear stress (WSS), suggesting desired vascular remodeling and restoration of WSS. In contrast, both NOS3+/+ and NOS3-/- AVFs have small lumen, disturbed velocity streamlines, high vorticity, and high venous WSS. AVF vein MMP9 protein expression was reduced at 21 days in NOS3 OE mice compared to NOS3+/+ and NOS3-/- mice (p=0.09). AVF vein average intima/media thickness ratio was significantly lower in NOS3 OE mice compared to NOS3+/+ and NOS3-/- mice (p<0.0001) at 21 days. cGMP levels were significantly higher in NOS3 OE AVFs vs NOS3-/- and NOS3+/+ AVFs (p=0.05)

Conclusion

Increased NOS3 expression improves AVF hemodynamics and remodeling and reduces neointimal hyperplasia development. Future interventions that target increasing NOS3 expression and NO delivery may be beneficial to improving AVF development.

Funding

  • Clinical Revenue Support