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Myovascular Mechanisms of Cardiac Growth and Regeneration

Award Number: R01HL157277
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Myovascular Mechanisms of Cardiac Growth and Regeneration - ABSTRACT: We, and others, have determined that cardiomyocyte (CM) proliferation is dependent on cardiac endothelial cells (CECs). Proliferating CECs are spatiotemporally coupled to proliferating CMs in the neonatal mouse heart; loss of CECs leads to decreased CM proliferation; and higher levels of the master angiogenic factor Vegfa promote cardiac growth in zebrafish, neonatal mice, and humans. Based on these studies, our overall hypothesis is that activated, proliferating CECs instruct CM proliferation. Here, we propose studies to determine how CECs promote CM proliferation. We will use scRNA-seq and spatial modeling to identify the specific subset of CECs physically associated with proliferating CMs; we will determine how Ezh2- mediated chromatin remodeling coordinates CEC activation with CM proliferation; and we will define the potency of CEC-induced growth factors to stimulate CM proliferation. This work will result in new cellular, epigenetic, and paracrine mechanisms for CEC-induced cardiac growth and has high potential to inform methods for therapeutic heart regeneration.


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: 2025 ( Subtotal = $460,524 )
2025	2025	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	000	4	1/3/2025	NON-COMPETING CONTINUATION	$460,524
														Subtotal = $460,524

Issue Date FY: 2024 ( Subtotal = $501,460 )
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	000	3	12/26/2023	NON-COMPETING CONTINUATION	$460,524
2024	2024	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	001	3	6/12/2024	NON-COMPETING CONTINUATION	$40,936
														Subtotal = $501,460

Issue Date FY: 2023 ( Subtotal = $527,793 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	001	2	3/6/2023	NON-COMPETING CONTINUATION	$52,779
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Cardiovascular Diseases Research	000	2	1/6/2023	NON-COMPETING CONTINUATION	$475,014
														Subtotal = $527,793

Issue Date FY: 2022 ( Subtotal = $539,063 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Cardiovascular Diseases Research	000	1	12/21/2021	NEW	$539,063
														Subtotal = $539,063

Grand Total All Awards = $2,028,840

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Myovascular Mechanisms of Cardiac Growth and Regeneration

Award Number: R01HL157277

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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