Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

The role of matrifibrocytes in a fibrotic-like response during myxomatous heart valve disease progression

Award Number: K99HL179261
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/11/2025
PERIOD OF PERFORMANCE END DATE: 07/31/2027

Group Awards By:

View Award Description

The role of matrifibrocytes in a fibrotic-like response during myxomatous heart valve disease progression - Project Summary Normal heart valve structure and composition are established by valve remodeling, starting at late embryonic stages, and continuing postnatally. Valve remodeling results in a stratified extracellular matrix (ECM), decreased cell density and reduction in cell proliferation. Congenital valve malformations include abnormalities in valve remodeling such as ECM disruption and disorganization. Congenital heart valve abnormalities due to ECM gene mutations and defects, often lead to myxomatous valve disease (MVD). Progressive MVD is characterized by collagen fiber fragmentation, replacement of mucopolysaccharides and proteoglycans, leaflet thickening, and insufficiency, but the mechanisms mediating progressive valve degeneration remain unknown and there are no therapies to prevent or reverse MVD. Recently, our group reported that, in an Fbn1C1041G/+ Marfan syndrome (MFS) mouse model, the ECM mechanics and morphological alterations of the mitral valve occur before functional abnormalities are detectable. Surprisingly, by 6-12 months, collagen fiber remodeling is increased with abnormal fiber organization suggesting a compensatory fibrotic response. We also observed induction of matrifibrocyte gene expression associated with collagen-rich connective tissue such as in myocardial scarring after infarction. In preliminary studies we also observed increased expression of pFAK, a nonconical focal adhesion kinase (FAK), in MVD at the time of increased collagen production and matrifibrocyte gene induction, suggestive of a mechanically regulated myofibroblast response. The role of matrifibrocytes and FAK activation in heart valve disease progression and compensation is unknown. Therefore, we hypothesize that stress activation and collagen overproduction in MFS mitral valves induce matrifibrocytes causing an intrinsic reparative response via activated FAK. We propose three aims to elucidate the role and function of matrifibrocytes in ECM remodeling, maturation and disease. 1: Determine the contributions of fibrotic ECM in MVD progression in mitral valves, 2: Determine if valvular interstitial cell (VICs) activation and matrifibrocyte differentiation occur in response to collagen production and tissue stiffness in mitral valves and 3: To determine if the fibrotic response in the mitral valve during homeostasis and MVD progression is mediated through FAK activation. The K99 portion of this proposal will be carried out in the lab of Dr. Katherine E. Yutzey, an expert in heart valve disease, and co-mentor Dr. Jeffery D. Molkentin, an expert in fibrotic remodeling of the heart. Under their guidance, I will carry out my in vitro (Aims 1-3A) experiments during the K99 phase and start my in vivo (Aims 1-3B) murine model experiments during the K99 phase and continue during the R00 phase. Overall, the comprehensive Aims proposed will provide me with the opportunity to develop an independent research program that will be instrumental in my success as a scientist. Moreover, the data generated will have important implications for cardiovascular science, specifically in development of new therapeutic targets for heart valve disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $118,632 )
2026	2026	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Cardiovascular Diseases Research	000	2	7/15/2026	NON-COMPETING CONTINUATION	$118,632
														Subtotal = $118,632

Issue Date FY: 2025 ( Subtotal = $118,632 )
2025	2025	CHILDRENS HOSPITAL MEDICAL CENTER	3333 BURNET AVE	CINCINNATI	OH	45229	HAMILTON	USA	Cardiovascular Diseases Research	000	1	8/6/2025	NEW	$118,632
														Subtotal = $118,632

Grand Total All Awards = $237,264

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The role of matrifibrocytes in a fibrotic-like response during myxomatous heart valve disease progression

Award Number: K99HL179261

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/11/2025

PERIOD OF PERFORMANCE END DATE: 07/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer