# Mechanotransduction and transcriptional regulation during artery development

> **NIH NIH R01** · STANFORD UNIVERSITY · 2024 · $117,942

## Abstract

PROJECT SUMMARY
 Heart disease, the most common cause of death, frequently arises from blocking blood flow to cardiac
muscle. Blood flow travels to the heart first through coronary arteries and then into a capillary network where
oxygen exchange occurs. One approach to treating heart disease has been to expand the capillary network,
but this has achieved limited success. Here, we propose to instead expand coronary artery networks and
promote the development of collateral arteries, which are a subtype of artery with the potential to form a natural
bypass. In the previous funding period, our laboratory discovered cellular and molecular mechanisms driving
coronary artery formation in the developing embryo, including how the transcription factor Dach1 supports
artery growth through regulating blood flow stimulated cell behaviors (Chang, 2017, Genes and Dev). We also
described how the chemokine CXCL12 triggers collateral artery formation in the injured heart during the
neonatal growth period (Das, 2019, Cell). We hypothesize that these developmental pathways can be utilized
to stimulate adult coronary artery regeneration and provide beneficial outcomes during cardiac injury and
disease. Preliminary studies activating Dach1 or CXCl12 in adults shows indications of enhanced recovery
following experimental myocardial infarction. We will use the following Aims to further explore their reparative
potential. Aim 1 will use tissue clearing, whole organ imaging technology, and computational modeling to
define how injury, Dach1 overexpression, and CXCL12 administration alter artery structure and affect blood
flow parameters. Aim 2 will use cardiac injury models to intensively study how Dach1- and CXCL12-induced
artery growth and collateral development enhance recovery post-myocardial infarction. Aim 3 will delve into
the mechanisms by which Dach1 stimulates artery endothelial cell differentiation and morphogenesis.
 This work is significant because delineating how developmental signals stimulate coronary artery
regeneration could ultimately contribute to therapeutic interventions for heart disease. The work is innovative
because it takes a new approach to revascularization—targeting artery differentiation rather than just the
microvasculature. It also further develops cutting edge experimental techniques such as adult whole organ
imaging and a novel in vitro endothelial cell differentiation model, which could ultimately benefit the
cardiovascular research community at large. Finally, successful completion of the Aims is ensured by the
interdisciplinary environment at Stanford University and collaborative track record between this group of
investigators (Drs. Kristy Red-Horse, Kyle Loh, Alison Marsden, and Daniel Bernstein). The proposed work
will enhance our knowledge on cardiovascular development and regeneration by illuminating the biology of
the hitherto-enigmatic collateral arteries, as well as how transcriptional regulators such as DACH1 determine
artery ...

## Key facts

- **NIH application ID:** 11119176
- **Project number:** 3R01HL128503-10S1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Mary Red-Horse
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $117,942
- **Award type:** 3
- **Project period:** 2015-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11119176

## Citation

> US National Institutes of Health, RePORTER application 11119176, Mechanotransduction and transcriptional regulation during artery development (3R01HL128503-10S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11119176. Licensed CC0.

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