# Hemodynamic Flow-Mediated Myocardial Reprogramming Impacts Cardiac Development

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $326,813

## Abstract

PROJECT SUMMARY
Cardiac morphogenesis is a complex process that is mediated by not only cellular, molecular and genetic
factors but also environmental influences, such as hemodynamic flow. Disruption in these developmental
events can result in Congenital Heart Disease (CHD), the most common birth defect in humans, which affects
nearly one out of every one-hundred live births and is responsible for the vast majority of prenatal losses.
Although several cardiac gene regulatory programs are known to play an important role in cardiac
development, specific disease-causing genes so far account for only ~10% of patients with CHD, suggesting
that additional genetic and environmental etiologies, including biophysical forces, may contribute toward this
disease. Thus, illuminating the cellular, molecular, and physiologic basis of how biophysical factors influence
cardiac morphogenesis may provide novel insights into the prevention, diagnosis, and treatment of patients
predisposed for CHD. Although recent studies have shown that biomechanical forces such as cardiomyocyte
contractility and intracardiac hemodynamic flow may regulate cardiac morphogenesis, the underlying
mechanisms of how these biophysical forces specifically contribute to various aspects of cardiac development
remains to be elucidated. Here, we propose that alterations in hemodynamic forces may impact
cardiomyocyte cell identity through an “adaptive cellular reprogramming” process where cardiomyocytes that
retain sufficient cellular plasticity are able to reprogram in order to change their cell fate in response to
environmental influences. Thus, the overall goals of these proposed studies are to illuminate how the heart
senses biomechanical forces and transduces their signal to control cardiomyocyte reprogramming. The results
of these studies will not only elucidate how hemodynamic forces may adaptively alter cardiomyocyte fate
during heart development to guide cardiac morphogenesis but also provide insight into how the heart may
reprogram cardiomyocytes in response to perturbations in hemodynamic flow due to structural or functional
heart defects.
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## Key facts

- **NIH application ID:** 9934874
- **Project number:** 5R01HD092216-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Neil C Chi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $326,813
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934874

## Citation

> US National Institutes of Health, RePORTER application 9934874, Hemodynamic Flow-Mediated Myocardial Reprogramming Impacts Cardiac Development (5R01HD092216-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9934874. Licensed CC0.

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