# Biomechanics of early mammalian cardiogenesis

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $543,451

## Abstract

PROJECT SUMMARY
 Human congenital heart defects (CHD) are very common, occurring in nearly 1% of
live births. Moreover, cardiovascular (CV) failures are the leading cause of birth defect-
related deaths in infants. It is well established that biomechanical stimuli are important
regulators of CV development. Thus, defining how mechanical factors are integrated
with genetic pathways to coordinate mammalian heart tube function and morphogenesis
is critically important for understanding CHD and heart failure. Such information will also
factor heavily into strategies for new therapeutic interventions to treat/prevent CHD.
Toward that end, the mouse model is an excellent system in which to study human
congenital defects. However, due to the internal nature of mammalian development,
analysis of heart biomechanics is challenging.
 Through the previous cycle of this grant, we established a set of innovative optical
coherence tomography (OCT) approaches for live, high-resolution 3D imaging and
quantitative assessment of mouse embryo CV dynamics. These techniques were
applied to analysis of the pumping mechanism of the E8.5 to E10.5 mouse heart and
characterization of mutant phenotypes mimicking human CHDs. Therefore, we are in a
unique position to investigate how mechanical stimuli of cardiodynamics and blood flow
are linked to molecular/genetic changes during early cardiac differentiation in living
mouse embryos.
 While multiple studies suggest that cardiac contraction, blood flow and stiffness each
influence CV development, due to the interdependence of these factors, their individual
roles are unknown. The goal of this proposal is to define the differential role of cardiac
contraction and flow-induced shear stress in regulating mechanical homeostasis
(stiffness) and cell fate decisions in vivo. These experiments will specifically address the
context-dependent interplay between these factors, which likely vary between cardiac
regions with different functional roles, such as in actively contracting regions versus the
passively contracting outflow tract (OFT).
 Scientific Premise, Scientific Rigor, and Relevant Biological Variables: This
proposal will fill a significant gap in the field of early mammalian cardiac development
and define the role of cardiac forces in maintaining mechanical homeostasis and cell
differentiation. This information will lead to a better understanding, prevention and
treatment of CHD and embryonic cardiac failures in humans. The proposed study is
supported by strong preliminary data. We carefully articulated the number of
experimental animals to be used, the precise genetic makeup of these animals, and the
rationale for the choice of the models. Sex as a biological variable is considered and
addressed in the proposal. Extensive details are provided to ensure that preliminary and
proposed experiments can be replicated in other laboratories.

## Key facts

- **NIH application ID:** 10428362
- **Project number:** 5R01HD096335-10
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Irina Larina
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $543,451
- **Award type:** 5
- **Project period:** 2018-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428362

## Citation

> US National Institutes of Health, RePORTER application 10428362, Biomechanics of early mammalian cardiogenesis (5R01HD096335-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10428362. Licensed CC0.

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