# Roles of neuropilin-1 in endothelial cell dysfunction

> **NIH NIH R01** · MAYO CLINIC  JACKSONVILLE · 2020 · $391,544

## Abstract

PROJECT SUMMARY/ABSTRACT
Heart failure with preserved ejection fraction (HFpEF) affects more than 3 million adults of the United States
and has no effective therapy. The promising effect of general strategies for improving endothelial cell (EC)
function in HFpEF patients has highlighted the crucial roles of EC dysfunction in the disease pathogenesis.
However, the molecular mechanism of EC dysfunction and how it contributes to the pathogenesis of HFpEF
are still poorly understood. A recent patient study identified serum neuropilin-1 (NRP1) as a prognostic marker
in HFpEF patients. Our preliminary data indicate that endothelial NRP1 is increased in the cardiac tissues of
murine HFpEF models and mice deficient of endothelial NRP1 show improved EC and cardiac diastolic
functions in these models. Tumor necrosis factor-α (TNFα) is a major inducer of EC dysfunction and
associates with the disease progression of HFpEF. Our preliminary data suggest that knockdown of NRP1
reduces TNFα-induced expression of adhesion molecules but enhances the levels of endothelial nitric oxide
synthase (eNOS) in ECs. Computational docking model and protein binding assay collectively indicate the
direct interaction between NRP1 and TNFα. Based on these results, this project will test the central hypothesis
that endothelial NRP1, acting as a novel co-receptor with TNFR, leads to the pathogenesis of HFpEF by
increasing cardiac inflammation and impairing myocardial nitric oxide bioavailability.
Two Specific Aims are proposed: Aim 1: Delineate the crosstalk between NRP1 and TNFα/TNFR in EC
dysfunction. We will characterize the interaction between NRP1 and TNFα/TNFR using microplate-based
binding assay and cultured ECs. The role of NRP1 in TNFα-induced EC dysfunction will be examined in both
mouse and zebrafish endothelial cell specific NRP1 knockout models. Aim 2: Reveal the role of endothelial
NRP1 in the pathogenesis of HFpEF. We will use mouse HFpEF models to investigate how endothelial NRP1
cooperates with TNFR1 to control the disease initiation and progression of HFpEF.

## Key facts

- **NIH application ID:** 10051013
- **Project number:** 1R01HL148339-01A1
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** Ying Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,544
- **Award type:** 1
- **Project period:** 2020-07-06 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051013

## Citation

> US National Institutes of Health, RePORTER application 10051013, Roles of neuropilin-1 in endothelial cell dysfunction (1R01HL148339-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10051013. Licensed CC0.

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