# Dissecting the role of the cardiac fibroblast in hypertrophy.

> **NIH NIH R01** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $596,819

## Abstract

Abstract
The cardiac myocyte has long been the primary focus of studies attempting to elucidate the
regulatory aspects underlying cardiac development and disease. However, recently the
involvement of nonmyocytes has emerged as potentially just as important as myocytes in
contributing to and controlling cardiac remodeling during progressive pathogenesis associated
with heart failure. More specifically, the cardiac fibroblast and its ability to convert to
myofibroblasts in promoting extracellular matrix (ECM) production, ventricular remodeling and the
fibrotic response is now viewed as an equally critical regulator of cardiac biology. Here we will
address how fibroblasts in the heart function as key determinants of disease and pathologic
remodeling. We have developed important genetic tools that specifically target the fibroblast in
the heart so that we can manipulate the activity of these cells. Thus, here we can now test the
novel hypothesis that activated fibroblasts (myofibroblasts) are critical regulators of cardiac
disease processes, not only involving fibrosis but also the ability of cardiomyocytes in the heart
to properly hypertrophy. We will test the more specific hypothesis that fibroblasts regulate the
density and integrity of the cardiac ECM and collagen that cardiomyocytes must sense as
increased structural support in order to effectively hypertrophy in vivo. Indeed, we further
hypothesize that the tension sensing mechanism within the cardiomyocyte extends outward to
the ECM and its integrity or stiffness. This application has 3 specific aims: 1) To increase the
structural rigor of collagen in the heart to investigate the impact on cardiomyocyte hypertrophic
growth potential in vivo, 2) To genetically impair type I collagen formation in the heart to reduce
ECM structural rigor, and 3) To examine the actin filamentous network as a central signaling
mechanism whereby ECM integrity or stiffness impacts myocyte growth in vivo. Collectively,
these specific aims will uncover how fibroblasts communicate with cardiomyocytes in the heart
through the ECM and its properties. Such an understanding will lay the foundation for future
studies into specific therapeutic targets in treating longstanding fibrotic heart disease states or
hypertrophy in general.

## Key facts

- **NIH application ID:** 10821390
- **Project number:** 5R01HL160765-03
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** Jeffery D Molkentin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $596,819
- **Award type:** 5
- **Project period:** 2022-07-18 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821390

## Citation

> US National Institutes of Health, RePORTER application 10821390, Dissecting the role of the cardiac fibroblast in hypertrophy. (5R01HL160765-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10821390. Licensed CC0.

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