Abstract: FR-PO999

Effects of Nitric Oxide Releasing Bionanomatrix Gel on Reducing Neointimal Hyperplasia and Inflammation

Session Information

Category: Bioengineering and Informatics

  • 101 Bioengineering and Informatics

Authors

  • Somarathna, Maheshika Srimali, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Hwang, Patrick, Endomimetics LLC, Birmingham, Alabama, United States
  • Isayeva Waldrop, Tatyana, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Alexander, Grant, The University of Alabama at Birmingham, Birmingham, Alabama, United States
  • Guo, Lingling, The University of Alabama at Birmingham, Birmingham, Alabama, 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

Vascular access is the lifeline for hemodialysis patients. An arteriovenous fistula (AVF) is the preferred type of vascular access. However, nearly 60% of the time, AVF maturation failure occurs due to early venous neointimal hyperplasia (NIH) formation and poor vascular remodeling. We hypothesize that local nitric oxide (NO) therapy administered at the time of AVF creation can inhibit venous NIH development and reduce local AVF inflammation. The aims of this study are to evaluate in a rat AVF model the effects of a NO-releasing bionanomatrix gel on: 1) NIH formation and 2) expression of inflammatory biomarkers such as MCP-1, IL-1, IL-6 and TNF-α in AVF vein.

Methods

Femoral vein to artery AVFs were created. After AVF creation, the NO-releasing gel was applied on the AVF anastomosis in 16 week old Sprague-Dawley rats (Figure 1). Rats were sacrificed at 7 days to perform: 1) Morphometric analysis of the AVF vein to access the changes in NIH development and 2) Western blot analysis from the vein segments to evaluate changes in expression levels of inflammatory biomarkers.

Results

The NO-releasing gel treatment group showed a significant reduction in NIH development at 7 days after AVF creation (Figure 1) when compared to the control group. MCP-1, IL-1, IL-6 and TNF-α protein expression in AVF vein was significantly lower in the NO-releasing gel treated group.

Conclusion

NO-releasing gel therapy applied locally on the AVF has great potential to promote AVF maturation by reducing NIH and mitigating local inflammation following AVF creation.

Funding

  • NIDDK Support