# The Role of Nitric oxide/cyclic Guanosine Monophosphate (NO/cGMP) Signaling in Arteriovenous Fistula Maturation

> **NIH NIH F31** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2021 · $39,302

## Abstract

PROJECT SUMMARY
There are currently over 700,000 end stage renal disease (ESRD) patients in the United States.
Approximately 70% of ESRD patients undergo hemodialysis as their primary kidney
replacement therapy. An arteriovenous fistula (AVF) is the preferred type of vascular access in
hemodialysis patients. However, nearly 60% of AVFs created develop AVF maturation failure
due to early venous neointimal hyperplasia formation and impaired outward vascular
remodeling. The pathological mechanisms underlying AVF maturation failure is poorly
understood. Therefore, a major unmet clinical need in the field is the lack of effective
therapies to treat and prevent AVF maturation failure. The central hypothesis of this study is
that AVF creation will result in dysregulation of nitric oxide (NO) and cGMP activity that will
disrupt proper AVF maturation by influencing AVF remodeling and neointimal hyperplasia
formation. Therefore, NO/cGMP signaling pathway is an important therapeutic target for
clinically successful AVF maturation. In order to study the role of NO and cGMP on AVF
maturation we will 1) test the hypothesis that locally delivered NO therapy at the time of AVF
creation will improve AVF maturation by inhibiting neointimal hyperplasia and enhance AVF
remodeling, and reduce local inflammation; 2) test the hypothesis that a selective PDE5A
inhibitor, which prevents cGMP degradation, administered before and after AVF creation, will
improve AVF outward remodeling and inhibit neointimal hyperplasia; and will be also beneficial
in the setting of chronic kidney disease (CKD), where AVFs are created in this clinical setting.
These aims will be achieved using a rodent AVF model that has (1) an identical anatomic
configuration to human AVF and (2) recapitulates the lesion of progressive venous neointimal
hyperplasia seen in human AVF. Our studies are expected to elucidate the pathologic
significance of NO/cGMP signaling pathway on AVF maturation as well as provide the basis to
develop novel therapeutic strategies to treat and prevent AVF maturation failure in hemodialysis
patients.

## Key facts

- **NIH application ID:** 10083108
- **Project number:** 5F31DK123977-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Maheshika Somarathna
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,302
- **Award type:** 5
- **Project period:** 2019-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10083108

## Citation

> US National Institutes of Health, RePORTER application 10083108, The Role of Nitric oxide/cyclic Guanosine Monophosphate (NO/cGMP) Signaling in Arteriovenous Fistula Maturation (5F31DK123977-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10083108. Licensed CC0.

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