# Differential redox regulation of vein and arterial smooth muscle cells in AVF stenosis

> **NIH NIH R56** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $200,000

## Abstract

(PLEASE KEEP IN WORD, DO NOT PDF)
Kidney failure impacts many, with 750,000 cases annually in the US and 2 million globally. Treatment options include kidney transplant or dialysis. Hemodialysis requires vascular access, often through arteriovenous fistulae (AVF) for improved long-term survival and reduced infection risk when compared to grafts and catheters.
Nevertheless, AVFs frequently mature inadequately, exceeding 50% within 6 months, leading to interventions and complications due to neointimal hyperplasia (NH) and inadequate outward remodeling. Vascular injury results in the phenotypic modulation of vascular smooth muscle cells (VSMCs), pathognomonic of NH. Oxidative stress emerges as a pivotal contributor to these downstream processes. Consequently, interventions aimed at mitigating oxidative stress through antioxidant therapies have the potential to enhance AVF maturation, especially since patients with kidney failure have elevated levels of oxidative stress.
Our hypothesis posits that Nrf-2 activation in VSMCs and in an in vivo mouse AVF stenosis model, particularly in uremia, can inhibit VSMC phenotypic changes, and reduce NH while promoting outward remodeling, thus improving AVF maturation. We will investigate this through:
Studying the effect of Nrf2 activation on the phenotype of VSMC 
Assessing a new local therapeutic approach that activates Nrf2 in a mouse AVF stenosis model.
Successful completion of this proposal holds the potential to alleviate clinical morbidity associated with AVF failure, which remains our foremost objective, driven by the pressing needs of our patients.

## Key facts

- **NIH application ID:** 11174188
- **Project number:** 1R56DK140967-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Edward M Bahnson
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $200,000
- **Award type:** 1
- **Project period:** 2024-09-17 → 2025-09-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11174188

## Citation

> US National Institutes of Health, RePORTER application 11174188, Differential redox regulation of vein and arterial smooth muscle cells in AVF stenosis (1R56DK140967-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11174188. Licensed CC0.

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