Hemodynamics and KLF2/4 regulate myxomatous valve pathogenesis
Active Project Grant Awarded Last action
- Award ID
- F30HL173955
- Recipient
-
The Trustees Of The University Of Pennsylvania UEI GM1XX56LEP58
- Awarding agency
-
National Heart Lung and Blood Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $359,945
Award facts
- Assistance listing
- 93.837 Cardiovascular Diseases Research
- Completion date 83% complete
- Place of performance
- Philadelphia, PA 19104, USA
Award details come from USAspending.gov.
Description
- Abstract
- 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).
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $38,097 | |
| Amendment | $564 | |
| Amendment | $53,974 | |
| Amendment | $53,974 | |
| Amendment | $1,280 | |
| Amendment | $1,280 | |
| Amendment | $52,694 | |
| Amendment | $52,694 | |
| Amendment | $0 | |
| Amendment | $52,694 | |
| Amendment | $0 | |
| Amendment | $52,694 | |
| Original award | $0 |
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Quick answers
Who received award F30HL173955?
F30HL173955 was awarded to The Trustees Of The University Of Pennsylvania by National Heart Lung and Blood Institute (National Institutes of Health) on September 29, 2024.
How much is award F30HL173955 worth?
$359,945 has been obligated on F30HL173955.
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