Why the study?
Effective pharmacological treatments for cardiac valve disease are lacking, and whether the lymphatic and venous valve transcription factors PROX1 and FOXC2 regulate cardiac valve development and disease was unknown.
Population
Prox1 ΔVEC mice, isolated valve cells, and human mitral valve prolapse and aortic valve insufficiency samples
Comparison
Conditional deletion of Prox1 vs controls
Design
Preclinical animal and in vitro mechanistic study with human tissue validation
Key result
PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain extracellular matrix composition and prevent myxomatous degeneration of cardiac valves in mouse models.
Authors
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Does not support clinical use of PROX1 modulation; leaves open therapeutic targeting of this pathway in human valve disease.
PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain extracellular matrix composition and prevent myxomatous degeneration of cardiac valves, suggesting a potential therapeutic target.
Ho et al. (2023) studied Cardiac valve disease (myxomatous degeneration). Prox1 deletion in valvular endothelial cells vs. Wild-type mice was evaluated on Valve structure and functioning (myxomatous degeneration and stenosis). PROX1 antagonizes PDGF-B signaling partially via FOXC2 to maintain extracellular matrix composition and prevent myxomatous degeneration of cardiac valves in mouse models.