# Mechanisms that Govern Vasculogenesis

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2022 · $46,910

## Abstract

PROJECT SUMMARY/ABSTRACT
Ischemic heart disease (IHD) is the leading cause of death in the world and current therapies are limited due to
the inability to promote remuscularization of the injured heart. In the absence of remuscularization, the injured
heart forms a scar following a myocardial infarction (MI) that can progress towards heart failure. Insufficient
vasculature and impaired perfusion are critical factors affecting the morbidity and mortality observed in IHD.
These cardiovascular diseases are chronic, debilitating, lethal and they warrant the development of novel
therapies. One approach is to promote vasculogenesis in order to enhance heart regeneration. Clinical trials
using exogenous factors to treat IHD have shown conflicting results that have been attributed to the inability of
such factors to drive vasculogenesis. Therefore, new therapies that can fully drive vasculogenesis for the
treatment of IHD are warranted. Our laboratory has shown that the ets variant factor 2 (ETV2) is a transcription
factor that is both necessary and sufficient for the development of hematoendothelial (HE) lineages as loss of
ETV2 is embryonically lethal due to the absence of all blood and vasculature. Recent evidence from our
laboratory suggests that ETV2 functions as a pioneer transcription factor for the HE lineage. Pioneer transcription
factors bind and relax condensed chromatin in order to drive gene expression changes necessary for the
development or specification of cell lineages. Our preliminary data shows that ETV2 physically interacts with
BRG1, a chromatin remodeling enzyme, which has been shown to collaborate with other pioneer transcription
factors in the development of different lineages. However, it remains unclear how ETV2-BRG1 interactions might
be related to HE development and the pioneer function of ETV2. Furthermore, overexpression of ETV2 has been
shown to reprogram fibroblasts into functional endothelial cells in vitro. However, it is not known whether ETV2
overexpression can be used in vivo in a large animal model to reprogram fibroblasts after a MI to enhance
vasculogenesis in order to treat IHD. Therefore, the overall goal of this proposal is to develop therapeutic
strategies for IHD by understanding the mechanisms that govern vasculogenesis. I hypothesize that ETV2 drives
HE lineage development in a BRG1 dependent fashion and that in vivo overexpression of ETV2 will enhance
cardiac regeneration by promoting vasculogenesis. I will test this hypothesis by pursuing the following aims: (1)
to define the role of BRG1 in the pioneer function of ETV2 in the HE lineage, and (2) to define the capacity of in
vivo reprogramming by ETV2 following cardiac injury using a swine model. Completion of these studies will
enhance our understanding of how ETV2, as a pioneer factor, targets and relaxes condensed chromatin in a
BRG1-dependent fashion to drive HE development and vasculogenesis. These studies will also identify new
mechanisms that can en...

## Key facts

- **NIH application ID:** 10475310
- **Project number:** 5F30HL152561-03
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** JAVIER SIERRA-PAGAN
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,910
- **Award type:** 5
- **Project period:** 2020-09-28 → 2023-10-27

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10475310

## Citation

> US National Institutes of Health, RePORTER application 10475310, Mechanisms that Govern Vasculogenesis (5F30HL152561-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10475310. Licensed CC0.

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