# Myeloid KLF2 mediates S-nitrosylation-driven vascular response to ischemic injury

> **NIH NIH F30** · CASE WESTERN RESERVE UNIVERSITY · 2020 · $50,520

## Abstract

PROJECT SUMMARY/ABSTRACT
Vascular occlusive disease poses an increasing burden on healthcare systems. Blockage of major arteries
causes severe ischemic damage to tissues, with the potential of limb loss, organ dysfunction, and death. As a
response to occlusion, however, collateral vessels are able to remodel to bypass the occlusion, a process
termed arteriogenesis. Accumulating evidence implicates myeloid cells as key mediators of this remodeling,
however the exact role these cells play in arteriogenesis remains unclear. Previous studies from our group
have identified KLF2 as a transcriptional regulator of myeloid cell activation, a process critical for effective
arteriogenesis. Nascent observations in our lab demonstrate that loss of KLF2 in the myeloid compartment
greatly enhances perfusion recovery following a model of hindlimb ischemia (HLI). In addition, these
differences appear to be greatly dependent on induction of the prominent inflammatory enzyme, inducible nitric
oxide synthase (iNOS). Modification of critical proteins in vascular cells by S-nitrosylation has been shown to
greatly affect functions crucial to vascular remodeling. These findings provide the basis for our central
hypothesis that KLF2 serves as a regulator of macrophage-mediated nitric oxide (NO) production that affects
the S-nitrosoproteome of endothelial and smooth muscle cells during occlusive injury. The proposed study will
vigorously interrogate the effects of myeloid-KLF2 on vascular remodeling. Specifically, we aim to examine
whether KLF2 serves as a nodal regulator of myeloid function during arteriogenesis, in part through its
regulation of NO production. To accomplish this goal, this study will utilize a wide range of biochemical,
molecular, and pharmacological techniques, including, but not limited to: in vivo models of arteriogenesis,
microCT imaging, pharmacological modulation of NO, and S-nitrosylation assays. Together, these studies will
provide crucial insight on the cellular and molecular processes leading to proper arteriogenesis and will provide
the foundation for interventions targeting vascular occlusion with the goal of reducing debilitating complications
for patients.

## Key facts

- **NIH application ID:** 9986879
- **Project number:** 5F30HL139014-04
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** David Ryan Sweet
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2017-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986879

## Citation

> US National Institutes of Health, RePORTER application 9986879, Myeloid KLF2 mediates S-nitrosylation-driven vascular response to ischemic injury (5F30HL139014-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9986879. Licensed CC0.

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