# Immune Mechanisms Regulating Cardiac Remodeling

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2022 · $736,429

## Abstract

Summary
Cardiovascular disease is the number cause of death in the United States. Most cardiovascular diseases are
associated with an increase in myocardial mass or cardiac hypertrophy. The heart responds to exercise and
other stress through an increase in cardiomyocyte in size in order to produce more force and cope with the
increased demand. In addition to signaling pathways that are activated within cardiomyocytes, other cellular
changes occur in response to cardiac stress. Some of these changes are adaptive but others are maladaptive.
Although many therapies are available for heart failure, we are still not able to prevent maladaptive changes in
response to stress. Prevention of maladaptive remodeling can lead to the ultimate avoidance of heart failure. We
have acquired preliminary data using innovative technologies showing that macrophages and B cells are
activated in the early adaptive phase in response to cardiac stress. Our hypothesis is that cardiac resident
macrophages promote adaptive, compensatory remodeling during cardiac stress in a process that is regulated
by B cells. Based on our preliminary findings, we are proposing to determine the role of macrophages in the
early adaptive phase of cardiac remodeling during pathological and physiological stress (Aim 1), investigate the
origins and mechanisms of resident macrophage activation during hypertrophy (Aim 2), and identify the
mechanisms by which B cells influence macrophage function during cardiac stress (Aim 3). Throughout the
proposal we will use innovative techniques, such as single-cell RNA sequencing and advanced imaging
strategies, to probe the role of macrophages and B cells in cardiac remodeling. The ultimate goal of the current
proposal is to identify a possible adaptive role of macrophage early during the remodeling process. Using these
discoveries, future research will focus on developing novel therapeutics to enhance adaptive remodeling and
inhibiting maladaptive remodeling. Given the impact of cardiovascular disease on overall health, this proposal
holds great promise for reducing the burden of cardiovascular disease on our society.

## Key facts

- **NIH application ID:** 10337133
- **Project number:** 5R01HL155993-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Xavier Revelo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $736,429
- **Award type:** 5
- **Project period:** 2021-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337133

## Citation

> US National Institutes of Health, RePORTER application 10337133, Immune Mechanisms Regulating Cardiac Remodeling (5R01HL155993-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10337133. Licensed CC0.

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