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Abstract: TH-PO302

Influence of Hemodynamic Changes on Venous Endothelial Cell Adaptation After Arteriovenous Fistula Creation

Session Information

Category: Dialysis

  • 703 Dialysis: Vascular Access

Authors

  • Lewis, Taylor G., Rosalind Franklin University of Medicine and Science Chicago Medical School, North Chicago, Illinois, United States
  • Isayeva Waldrop, Tatyana, The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Somarathna, Maheshika Srimali, The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Ingle, Kevin Andrew, The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
  • Lee, Timmy C., The University of Alabama at Birmingham Department of Medicine, Birmingham, Alabama, United States
Background

The arteriovenous fistula (AVF) is considered the lifeline for ESRD patients, but AVF non-maturation is currently a great problem facing vascular access. Maturation is influenced by both hemodynamic changes and the uremic syndrome. Impaired vessel dilatation is the major characteristic of endothelial dysfunction, predominately explained by a decrease in bioavailable nitric oxide (NO) produced by eNOS. In response to oscillatory shear stress, immediate activation of the MCP1 gene results in monocyte adhesion to inflamed endothelium. The goal of this study is to evaluate the influence of hemodynamics on endothelial function using both in vivo and in vitro systems.

Methods

For the in vivo system, femoral end-to-side AVFs were created in rats. 7 days after creation, the AVFs and contralateral control veins were harvested, sectioned, and stained for eNOS expression. Samples were harvested for western blot analysis of MCP1 and eNOS protein expression. For the in vitro system, human umbilical venous endothelial cells (HUVECs) were cultured in silicone vessel-like structures set to mimic either laminar (LSS) or oscillatory (OSS) shear stress. HUVECs were isolated and stained for eNOS and MCP1 expression. Additionally, samples were isolated for western blot analysis of MCP1 and eNOS protein expression.

Results

In vivo AVF samples displayed less eNOS staining compared to contralateral vein samples. Western blot shows significantly greater eNOS expression in control veins (control=0.347, AVF=0.286, p=0.043) and significantly greater MCP1 expression in AVF veins (control=0.181, AVF=0.599, p=0.0002). In HUVECs, eNOS expression was significantly greater in LSS (eNOS=77.85, MCP1=22.49 µ2/nuclei, p=0.0061) and MCP1 expression was significantly greater in OSS (eNOS=54.83, MCP1=449.5 µ2/nuclei, p=0.0049). Western blot shows significantly greater eNOS expression under LSS (LSS=0.345, OSS=0.263, p=0.023) and significantly greater MCP1 expression under OSS (LSS=0.369, OSS=0.689, p=0.033).

Conclusion

In in vitro and in vivo studies, disturbed flow reduces eNOS production and increases inflammation as evidenced by increased levels of MCP-1 in the venous endothelium. Therapies that enhance endothelial function and reduce inflammation in the setting of disturbed flow may reduce AVF maturation failure.

Funding

  • NIDDK Support