# Hemodynamics and KLF2/4 regulate myxomatous valve pathogenesis

> **NIH NIH F30** · UNIVERSITY OF PENNSYLVANIA · 2024 · $53,974

## Abstract

Project Summary
Myxomatous valve disease (MVD) is among the most common types of cardiac valve disease and carries
significant morbidity and mortality, leading to regurgitation and valve prolapse. While most of the research efforts
at understanding MVD pathogenesis have focused on mouse models of syndromic MVD, the majority of MVD
patients lack known syndromic mutations and present later in life, suggesting that MVD is more often acquired
and likely influenced by environmental factors. We have recently demonstrated that hemodynamic shear forces
direct cardiac valve development through transcription factors KLF2 and KLF4, but the role of hemodynamic
forces and KLF2/4 in regulating mature valve homeostasis remains unexplored. Preliminary studies indicate that
genetic inducible loss of KLF2/4 from valve endothelial cells (VEC) results in a phenotype highly concordant with
human MVD. Importantly, similar MVD pathology results from transplanted hearts with loss of blood flow across
the mitral valve. Together, these results suggest a role for hemodynamic forces and KLF2/4 as critical regulators
of valve homeostasis. This proposal aims to characterize the role of hemodynamic forces in maintaining valve
homeostasis (Aim 1), identify specific targets of VEC KLF2/4 (Aim 2) and determine whether TGFß/Smad
signaling is a shared requirement for myxomatous pathology in models of both syndromic and acquired MVD
(Aim 3).

## Key facts

- **NIH application ID:** 10899120
- **Project number:** 1F30HL173955-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jesse Pace
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $53,974
- **Award type:** 1
- **Project period:** 2024-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899120

## Citation

> US National Institutes of Health, RePORTER application 10899120, Hemodynamics and KLF2/4 regulate myxomatous valve pathogenesis (1F30HL173955-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10899120. Licensed CC0.

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