# Specification and Function of Tissue Resident and Recruited Macrophages in Cardiac Remodeling and Heart Failure

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2022 · $787,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Groundbreaking discoveries resulting in the “immuno-revolution” have established the importance of
immunology across medical disciplines. Inflammation has long been considered as an important mechanism
contributing to the progression of ischemic and nonischemic forms of heart failure. Countless studies have
reported associations between numerous serum cytokines, adverse left ventricular remodeling, and patient
outcomes in the settings of chronic heart failure and myocardial infarction. While these observations highlight
the potential utility of suppressing inflammation in the heart, early clinical studies investigating anti-
inflammatory therapies in patients who experienced a myocardial infarction (corticosteroids) or those with
chronic heart failure (corticosteroids, TNF blockade) revealed disappointing results and dampened enthusiasm
around further drug development. At that time, limited information existed regarding the precise immune cell
types that promote disease and the signaling mechanisms that exert their effects.
In recent years, a renewed interest in targeting the immune system in cardiovascular disease has emerged.
This resurgence is powered by the discovery of the cellular mediators of inflammation in the heart and the
identification of the mechanisms that orchestrate their activation and damaging effector functions. These
findings exemplify the exciting, but unmet, opportunity to effectively target the immune system and improve
outcomes for individuals with cardiac diseases.
The proposed research program will built upon our laboratory’s prior accomplishments that have uncovered
remarkable diversity amongst the composition and function of macrophages in the healthy, failing, and
transplanted heart. We will integrate 3 active projects into a unified research program that aims to 1) dissect
new biological mechanisms governing cardiac macrophage diversity and function, and 2) translate our findings
into new diagnostic and therapeutic approaches to abrogate heart failure pathogenesis, potentiate functional
recovery of the failing heart, and prevent heart transplant rejection. Key themes will include the roles of
mechanosensing, inflammatory signaling, and monocyte fate specification in the pathogenesis of heart failure
across disease etiologies, cardiac tissue repair and recovery, and heart transplant rejection.

## Key facts

- **NIH application ID:** 10352659
- **Project number:** 1R35HL161185-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Kory J. Lavine
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $787,500
- **Award type:** 1
- **Project period:** 2022-01-15 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10352659

## Citation

> US National Institutes of Health, RePORTER application 10352659, Specification and Function of Tissue Resident and Recruited Macrophages in Cardiac Remodeling and Heart Failure (1R35HL161185-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10352659. Licensed CC0.

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