Monday, June 30, 2025 6/30/2025

Role of Adiponectin in Reversal of Age-related Vascular Dysfunction

Award Number: R01HL166591
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 02/15/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Role of Adiponectin in Reversal of Age-related Vascular Dysfunction - Aging is a primary risk factor for development of cardiovascular dysfunction and disease. The hallmarks of vascular aging are endothelial dysfunction, development of a synthetic, atherosclerotic phenotype in smooth muscle, and arterial inflammation and stiffening. We have shown that aerobic exercise training can mitigate or reverse age-related vascular dysfunction and adverse arterial remodeling; however, the cellular signals that contribute to the ability of exercise training to promote macro- and microvascular resiliency remain unidentified. Similarly, the mechanisms whereby exercise training reverses age- related vascular dysfunction remain unknown. Reduced circulating adiponectin has been associated with the adverse vascular changes that occur with advancing age; however, a role for adiponectin in age- related vascular dysfunction has not been demonstrated. We have reported that circulating adiponectin levels increase in response to late-life exercise training; however, a direct role for adiponectin signaling in reversal of age-related vascular dysfunction by exercise training has not been demonstrated. We propose to test a central hypothesis that 1) loss of adiponectin is a critical contributor to age- related vascular dysfunction and adverse arterial remodeling, and 2) adiponectin contributes to the ability of exercise training to promote vascular resiliency and reverse age-related vascular dysfunction and age-related adverse vascular remodeling. We propose to study sedentary and exercise trained mice, across the murine lifespan, to determine 1) the impact of loss- and gain-of-function of adiponectin on ceramide/sphingosine signaling in the endothelium of the microvasculature of the heart and skeletal muscle, 2) the impact of loss- and gain-of-function of adiponectin on development of a senescence-associated synthetic phenotype in vascular smooth muscle and contractile dysfunction the microvasculature of the heart and skeletal muscle, and 3) the impact of loss- and gain-of-function of adiponectin on remodeling of large arteries. Results from the proposed work will increase our understanding of the role of adiponectin in age-related vascular dysfunction and exercise training-induced reversal of age-related vascular dysfunction. A top biomedical research priority is to identify strategies which promote vascular resiliency with advancing age or which reverse age-related vascular dysfunction. The proposed work could identify 1) components of the adiponectin signaling pathway that could be targeted for prevention of age-related vascular dysfunction, and 2) novel exercise mimetics that could be employed for 1) promotion of vascular resiliency across the lifespan, and/or 2) reversal of age-related vascular dysfunction.


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 = $358,937 )
2025	2025	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Cardiovascular Diseases Research	000	4	11/20/2024	NON-COMPETING CONTINUATION	$358,937
2025	2024	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Cardiovascular Diseases Research	002	3	12/4/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$23,485
2025	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Cardiovascular Diseases Research	001	2	12/4/2024	NON-COMPETING CONTINUATION	-$23,485
														Subtotal = $358,937

Issue Date FY: 2024 ( Subtotal = $456,542 )
2024	2024	KANSAS STATE UNIVERSITY	1601 VATTIER STREET	MANHATTAN	KS	66506	RILEY	USA	Cardiovascular Diseases Research	003	3	8/27/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$322,722
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Cardiovascular Diseases Research	001	2	6/21/2024	NON-COMPETING CONTINUATION	$37,268
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Cardiovascular Diseases Research	002	2	8/26/2024	NON-COMPETING CONTINUATION	-$322,722
2024	2024	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Cardiovascular Diseases Research	000	2	11/16/2023	NON-COMPETING CONTINUATION	$419,274
														Subtotal = $456,542

Issue Date FY: 2023 ( Subtotal = $520,859 )
2023	2023	FLORIDA STATE UNIVERSITY	874 TRADITIONS WAY	TALLAHASSEE	FL	32306	LEON	USA	Cardiovascular Diseases Research	000	1	2/10/2023	NEW	$520,859
														Subtotal = $520,859

Grand Total All Awards = $1,336,338

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Role of Adiponectin in Reversal of Age-related Vascular Dysfunction

Award Number: R01HL166591

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 02/15/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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