# Distinct Pathways of VPF/VEGF Receptors

> **NIH NIH R01** · MAYO CLINIC  JACKSONVILLE · 2020 · $512,279

## Abstract

Abstract:
The long term objective of this application to understand distinct signaling pathways of vascular endothelial
growth factor (VEGF), also know as vascular permeability factor (VPF) receptors, in the pathogenesis of
cardiovascular disease. We now know that VEGF receptors are not only expressed in endothelial cells (ECs)
but are expressed in several non-endothelial cells like stem cells where they control pathophysiological non-
angiogenesis processes. In this grant cycle we will focus on how VEGF-B and its receptors, neuropilin-1
(NRP1) in cardiomyocytes play a protective role in cardiomyopathy, whereas in endothelial cells NRP1 in
connection with IFNγR1 promotes proinflammatory response. To test our hypothesis, we have proposed
three specific aims. In Aim 1, we will examine the molecular pathways of VEGF-B/NRP1-mediated
cardioprotection in CMs both in vitro and in two different cardiomyopathy disease process, myocardial
infarction (MI) and virus induced-inflammatory cardiomyopathy (myocarditis) in both mouse and zebrafish
models. In Aim 2, we will investigate the role of endothelial cell NRP1 (NRP1EC) in MI and myocarditis using
an inducible EC-specific NRP1 knockout mice and zebrafish models. We will also define the regulatory role
of IFNγ/NRP1EC on inflammatory chemokines in cardiac ECs and related downstream signaling pathwya.
Finally, in Aim 3 we will test whether we can treat inflammatory cardiac diseases by boosting mitochondrial
function. In this regard, we will use (-) Epicatechin (Epi), which promotes mitochondrial function, to reverse
the inflammation and cardiomyopathy in the two models. Epi is derived from plant-based chemicals,
particularly from cocoa. Secondly, we will also use anti-CXCL10 antibodies to inhibit the inflammatory
responses in similar models. Finally we will test whether combining both Epi and anti-CXCL10
antibody can inhibit advance stages of cardiomyopathy. Overall our proposed study will reveal the
molecular mechanism of VEGF-B/NRP1CM as well IFNγR1/NRP1EC signaling in MI and myocarditis and will
identify a novel treatment strategy for patients with cardiomyopathy. In addition, the unique pathways and
therapeutic strategies that will be developed in this proposal may apply to other chronic inflammatory
conditions that affect the heart like atherosclerosis and autoimmune diseases.

## Key facts

- **NIH application ID:** 9841983
- **Project number:** 5R01HL140411-03
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** DEBABRATA MUKHOPADHYAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $512,279
- **Award type:** 5
- **Project period:** 2017-12-08 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841983

## Citation

> US National Institutes of Health, RePORTER application 9841983, Distinct Pathways of VPF/VEGF Receptors (5R01HL140411-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9841983. Licensed CC0.

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