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Dynamic Role of Hyaluronan in Ventricular Remodeling

Award Number: F31HL162518
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 02/01/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Dynamic Role of Hyaluronan in Ventricular Remodeling - Project Abstract The extracellular matrix (ECM) provides structural and functional support for the myocardium; however, heart failure alters the composition of the ECM. The ECM is composed of a number of proteins, lipids, and saccharides, yet their function is largely unknown. We found that one of the most abundant components of the ECM, hyaluronan (HA), accumulates following myocardial infarction; however, the role of HA following during infarct- induced heart failure is not known. Fibroblasts are a major cell type involved in ventricular remodeling. Once activated, fibroblasts proliferate and produce ECM components, such as collagen and HA. These events are associated with acute scar formation and chronic ventricular remodeling. In this project, I will explore the extent to which fibroblast-derived HA impacts the extracellular matrix. Specifically, I will study fibroblasts collagen secretion when HA metabolism is manipulated. Additionally, I will examine the extent to which fibroblast-derived HA contributes to acute scar formation post-MI. Finally, I will determine the extent to which fibroblast-derived hyaluronan contributes to chronic ventricular remodeling. We contend that acute increases in HA accumulation are required for scar formation following acute MI; however, the persistent, excessive production of HA provokes fibrosis beyond the initial scar. Hence, we predict that HA has a dynamic role following infarct-induced heart failure: beneficial early and maladaptive late. Taken together, these studies will provide novel insight into the role of HA in collagen secretion, acure scar formation, and chronic fibrosis. With this fundamental knowledge, we can, in future studies, explore therapeutic approaches. Regardless of the specific findings of this research plan, this fellowship will serve as an excellent vehicle to enhance my training so I can eventually become an independent scientist leading my own research laboratory. The combination of the experimental plan, experimental tools, my sponsor, the environment, advanced coursework, and professional development opportunities creates a high likelihood for me to realize my eventual goals and contribute significantly to the literature in the process.


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 = -$2,194 )
2026	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	000	4	3/24/2026	NON-COMPETING CONTINUATION	-$2,194
														Subtotal = -$2,194

Issue Date FY: 2025 ( Subtotal = $9,991 )
2025	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	004	4	9/16/2025	NON-COMPETING CONTINUATION	$141
2025	2025	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	003	4	1/9/2025	NON-COMPETING CONTINUATION	$9,850
2025	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	002	3	1/8/2025	NON-COMPETING CONTINUATION	$0
2025	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	001	2	1/8/2025	NON-COMPETING CONTINUATION	$0
2025	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	000	1	1/8/2025	NEW	$0
														Subtotal = $9,991

Issue Date FY: 2024 ( Subtotal = $35,858 )
2024	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	000	3	2/1/2024	NON-COMPETING CONTINUATION	$34,578
2024	2024	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	001	3	9/5/2024	NON-COMPETING CONTINUATION	$1,280
														Subtotal = $35,858

Issue Date FY: 2023 ( Subtotal = $34,578 )
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	001	2	4/22/2023	NON-COMPETING CONTINUATION	$942
2023	2023	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	000	2	2/1/2023	NON-COMPETING CONTINUATION	$33,636
														Subtotal = $34,578

Issue Date FY: 2022 ( Subtotal = $33,636 )
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	002	1	6/7/2022	NEW	$716
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	000	1	1/14/2022	NEW	$32,920
2022	2022	UNIVERSITY OF LOUISVILLE	2301 S 3RD ST	LOUISVILLE	KY	40208	JEFFERSON	USA	Cardiovascular Diseases Research	001	1	1/14/2022	NEW	$0
														Subtotal = $33,636

Grand Total All Awards = $111,869

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Dynamic Role of Hyaluronan in Ventricular Remodeling

Award Number: F31HL162518

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 02/01/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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