# Distinct Pathways of VPF/VEGF Receptors

> **NIH NIH R01** · MAYO CLINIC  JACKSONVILLE · 2024 · $667,504

## Abstract

Project Summary
The long-term objective of this application is to understand the molecular pathways of myocardial infraction (MI)-
mediated cardiac fibrosis and eventually heart failure. In our last grant cycle, we elucidated thoroughly the role
of Neuropilin-1 (NRP1), a multi-ligand receptor/adaptor and mediator of different signaling pathways including
TGFβ, in MI-induced cardiac pathogenesis, in particular fibrosis, and inflammation. Our preliminary data suggest
that conditional knockdown of NRP1 in the adult mice, either in cardiomyocytes (CM) or in endothelial cells (EC)
resulted varied phenotypes following cardiac injury (MI). In addition, our preliminary data from the single-nucleus
RNA sequencing (snRNA seq) using the cardiac tissues in a cell-specific manner and revealed marked changes
in gene expression patterns of key genes previously known to be associated with inflammation, cardiac
hypertrophy, fibrosis. In addition, we revealed microRNA (miR30s) showed differentially expressed in ECNRP1-/-
vs. CMNRP1-/- cells that correlated with HF genes. Hence, the scientific premise of this proposal is to reveal the
mechanistic role of divergent NRP1 spatiotemporal signaling in MI pathogenesis, and eventually to develop new
therapeutic targets and strategies to overcome progressive cardiac dysfunctions and overall heart failure. In this
regard, we will examine the spatiotemporal influence of NRP1 pathways for cardiac fibrosis following MI injury
as well as define the tissue-specific role of microRNAs regulated by NRP1 pathways on MI-induced fibrosis.
Finally, we will develop new therapeutic approaches to overcome cardio fibrosis following MI injury combining
novel NRP1 inhibitor (NRP1i) using novel targeted liposomal formulations. The current application is a multi-
disciplinary approach to reveal the spatiotemporal role of NRP1 in cardiac fibrosis/remodeling and identify new
targets to develop novel therapies to overcome one of the most common myocardial pathologies, which is an
unmet clinical need.

## Key facts

- **NIH application ID:** 10882957
- **Project number:** 2R01HL140411-05A1
- **Recipient organization:** MAYO CLINIC  JACKSONVILLE
- **Principal Investigator:** DEBABRATA MUKHOPADHYAY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $667,504
- **Award type:** 2
- **Project period:** 2017-12-08 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10882957

## Citation

> US National Institutes of Health, RePORTER application 10882957, Distinct Pathways of VPF/VEGF Receptors (2R01HL140411-05A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10882957. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*