# Regulation of cardiac inflammation by fibroblasts

> **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 2021 · $538,806

## Abstract

Abstract
Heart failure is a progressive disease that is often exacerbated by inappropriate cardiac remodeling in
response to stress. However, therapies that can efficiently target fibrosis, a key component of
pathologic remodeling, are currently unavailable. While an inflammatory response after acute injury is
essential for clearing dead tissue, and some fibrosis may be necessary to maintain the tensile
strength of injured myocardium, a sustained inflammatory response can lead to inappropriate
amounts of fibrosis. Several resident cardiac cell populations have been implicated in regulating the
composition and activation of immune cells after acute heart injury, but the role of cardiac fibroblasts
in this process is poorly understood. The goal of these studies is to elucidate the role that fibroblasts
play in regulating inflammation. Our preliminary data demonstrate that initial innate immune
responses proceed normally in the absence of fibroblasts, but populations of inflammatory cells
persist longer than when in the presence of fibroblasts. We hypothesize that Ras signaling in cardiac
fibroblasts directs anti-inflammatory gene expression later in the remodeling process and identification
of these pathways will permit the differentiation of pathogenic and regenerative remodeling. In Aim I,
we will use cardiac fibroblast ablation to identify the timing of anti-inflammatory signals. We will then
determine the specific anti-inflammatory regulators. In Aim II, we will manipulate Ras signaling in
fibroblasts to determine how alteration of this pathway controls inflammatory cell infiltration, activation,
and subsequent remodeling. In Aim III, we will determine if these inflammatory regulators are
conserved in human cardiac fibroblasts. This project will provide novel insights into the role that
cardiac fibroblasts play in immune regulation after cardiac injury, and identify signaling pathways that
may be therapeutically modulated to limit pathologic remodeling.

## Key facts

- **NIH application ID:** 10238764
- **Project number:** 5R01HL144067-04
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** Michelle D Tallquist
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $538,806
- **Award type:** 5
- **Project period:** 2018-08-11 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10238764

## Citation

> US National Institutes of Health, RePORTER application 10238764, Regulation of cardiac inflammation by fibroblasts (5R01HL144067-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10238764. Licensed CC0.

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