Scientific Reports (Dec 2023)

Effects of endothelial nitric oxide synthase on mouse arteriovenous fistula hemodynamics

  • Shelly Baltazar,
  • Hannah Northrup,
  • Joshua Chang,
  • Maheshika Somarathna,
  • Tatyana Isayeva Waldrop,
  • Timmy Lee,
  • Yan-Ting Shiu

DOI
https://doi.org/10.1038/s41598-023-49573-5
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 12

Abstract

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Abstract Newly created arteriovenous fistulas (AVFs) often fail to mature for dialysis use due to disturbed blood flow at and near the AVF anastomosis. The disturbed flow inhibits the endothelial nitric oxide synthase (NOS3) pathway, thus decreasing the production of nitric oxide, a vasodilator. Previously, our group reported that NOS3 expression levels affect AVF lumen size in a mouse model. In this study, we performed MRI-based computational fluid dynamics simulations to investigate the hemodynamical parameters (velocity, wall shear stress (WSS), and vorticity) in a mouse AVF model at day 7 and day 21 post-AVF creation using three NOS3 strains: overexpression (OE), knockout (KO), and wild-type (WT) control. This study is the first to reveal hemodynamics over time in mouse AVFs, consider spatial heterogeneity along the vein, and reveal the effect of NOS3 on the natural history of mouse AVF hemodynamics. From day 7 to day 21, OE has smoother streamlines and had significantly lower vorticity and WSS than WT and KO, suggesting that WSS was attempting to return to pre-surgery baseline, respectively. Our results conclude that the overexpression of NOS3 leads to desired optimal hemodynamics during AVF remodeling. Future studies can investigate enhancing the NOS3 pathway to improve AVF development.