# Role of the Epicardium in Valve Development and Valve Disease

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $487,800

## Abstract

In this project we aim to determine the role of epicardially-derived cells (EPDCs) in the formation
of the atrioventricular (AV) valves and to investigate their potential role in the pathogenesis of
myxomatous valve disease (MVD). A few years ago, we published a study in which we described
how EPDCs at the atrioventricular (AV) junction contribute to a specific set of leaflets of the AV
valves. To obtain insight into how these events are regulated, we initially focused on growth factor
signaling through the Bone Morphogenetic Protein (BMP) pathway. We deleted the BMP receptor
ALK3/BMPR1A from the epicardial cell lineage using the epicardial-specific WT1cre mouse. We
observed that this led to abnormalities at the AV junction, including a significant decrease in the
number of AV-EPDCs in the lateral valve leaflets. We also found that, after birth, the valves
developed a myxomatous valve phenotype, reminiscent of that being observed in patients
suffering MVD. Deleting the transcription factor SOX9 from the epicardial cell lineage led to similar
results. The goals of this project are to determine the mechanisms regulating the migration of AV-
EPDCs into the parietal AV valve leaflet, to establish how AV-EPDCs regulate AV valve
development, and to elucidate their role in the pathogenesis of mitral valve disease.

## Key facts

- **NIH application ID:** 10418935
- **Project number:** 1R01HL162913-01
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Arno Wessels
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $487,800
- **Award type:** 1
- **Project period:** 2022-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418935

## Citation

> US National Institutes of Health, RePORTER application 10418935, Role of the Epicardium in Valve Development and Valve Disease (1R01HL162913-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10418935. Licensed CC0.

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