# Mechanisms of ER71/ETV2-regulated Vascularization

> **NIH NIH R01** · LOUISIANA STATE UNIV HSC SHREVEPORT · 2020 · $365,000

## Abstract

Abstract
Our understanding on the cardiovascular system has been widened over the past decades, but still millions of
patients with cardiovascular disease (CVD), the most devastating disease in the United States and the rest of
the world, await more effective means to treat the disease. Thus, a comprehensive insight into the
mechanisms regulating the function of the cardiovascular system is urgently needed. Previously, we have
demonstrated an indispensable role of the transcription factor ETV2 (also known as ER71) in cardiovascular
system development. Also, our recent studies with genetically modified mice provide compelling evidence that
show ETV2’s potent and novel functions in the vascular regeneration in adults. Mice lacking endothelial ETV2
exhibit significantly impaired new vessel formation in response to tissue injuries including laser-induced eye
injury, skin wounding, or hindlimb ischemic injury, which are models for age-related macular degeneration,
general wound healing, and peripheral arterial disease, respectively. Moreover, a lentiviral delivery of ETV2
into ischemic hindlimbs leads to an improved recovery of blood flow, augments angiogenic gene expression
and enhances vascular regeneration, highlighting a requisite postnatal function of ETV2 in an injury-induced
neovascularization. However, current knowledge on mechanisms by which ETV2 functions in the
cardiovascular system and vascular regeneration is very limited. Our preliminary results suggest that ETV2
directs the expression of endothelial genes and thus generation of cardiovascular lineages by regulating the
status of H3K9 methylation though the interaction with KDM4A, a histone demethylase. In addition, our
investigations strongly suggest a functional correlation between the NFB pathway and ETV2 in mediating
injury-induced neovascularization. Furthermore, we have several lines of evidence showing that
myelomonocyte ETV2 plays a significant role in neovascularization upon ischemic insults. Building upon these
strong and novel evidence as well as tools, we will decipher mechanisms and functions of ETV2, 1) by
determining the epigenetic regulatory role of the interaction between ETV2 and KDM4A for cardiovascular
lineage generation, 2) by investigating the role of the NFB as a direct upstream regulator of ETV2 in mouse
models of hindlimb ischemia and tumor, 3) by revealing the novel functions of myelomonocyte ETV2,
contributing to neovascularization by regulating inflammation. The outcome of this work will reveal uncovered
functions of ETV2 in vascular development and functions as well as tissue repair, significantly advancing our
limited knowledge on vascular biology. Thus, our findings could lead to the development of novel, effective
therapeutic strategies for diseases related to dysfunctional vessel formation, an important translational aspect
of the proposed studies.

## Key facts

- **NIH application ID:** 10129642
- **Project number:** 7R01HL119291-07
- **Recipient organization:** LOUISIANA STATE UNIV HSC SHREVEPORT
- **Principal Investigator:** Changwon Park
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $365,000
- **Award type:** 7
- **Project period:** 2013-08-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10129642

## Citation

> US National Institutes of Health, RePORTER application 10129642, Mechanisms of ER71/ETV2-regulated Vascularization (7R01HL119291-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10129642. Licensed CC0.

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