# Functional heterogeneity of cardiac reparative cells after injury

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $394,652

## Abstract

PROJECT SUMMARY
Cell lineage tracing and fate mapping methods have identified multiple origins of
progenitor cells, macrophages and extracellular matrix (ECM)-producing cells that
become mobilized after injury to repair cardiac tissue. These studies also revealed, that
in the disease environment, resident cells become plastic, changing their stereotypical
identities to adopt pro-inflammatory and pro-fibrotic phenotypes. At present, the
functional significance of this heterogeneity among reparative cells is poorly understood.
We recently demonstrated that vascular endothelial cells are a major source of cardiac
cell heterogeneity, supplying about 40% of Sca1+ progenitor cells that reside in the
adventitia of coronary arteries during homeostasis, and 30% of ECM-producing cells
after acute ischemic injury. Vascular inflammation is a key trigger of endothelial
plasticity in pathological conditions. We discovered that the BMP antagonist Grem2
limits the magnitude of the inflammatory response by suppressing the pro-inflammatory
phenotype of endothelial cells. We hypothesize that reparative cells of diverse origins
play distinct roles after cardiac injury, and that inflammatory processes and BMP
signaling affect their plasticity and fate decisions in the adult heart.
To test these concepts, we will determine molecular signatures, spatiotemporal
distribution and ECM production characteristics among ECM-producing cell populations
of distinct origins after acute ischemic injury, investigate the role of inflammation and
BMP signaling in EC plasticity, and, assess whether the origin of Sca1+ cardiac
progenitor cells dictates their function.
Cardiovascular diseases are responsible for the majority of deaths in the U.S. and
worldwide. The proposed research will establish mechanisms that control cellular
plasticity and fate decisions of cardiac repair cells in the disease environment. From a
clinical perspective, our findings will provide new targets to favorably manipulate cardiac
tissue repair in order to limit ventricular remodeling and prevent heart failure.

## Key facts

- **NIH application ID:** 9947992
- **Project number:** 5R01HL138519-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** ANTONIS HATZOPOULOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $394,652
- **Award type:** 5
- **Project period:** 2017-07-15 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9947992

## Citation

> US National Institutes of Health, RePORTER application 9947992, Functional heterogeneity of cardiac reparative cells after injury (5R01HL138519-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9947992. Licensed CC0.

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