Tuesday, July 1, 2025 7/1/2025

Novel Role of Interleukin-17 in Sympathetic Activation in Heart Failure

Award Number: R01HL155091
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/08/2021
PERIOD OF PERFORMANCE END DATE: 12/31/2025

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Novel Role of Interleukin-17 in Sympathetic Activation in Heart Failure - Heart failure (HF) is the most common reason for hospitalization and death among those older than 65 years, and statistic is projected to grow as our population ages. The socioeconomic impact of HF on our health care system is enormous. Development of innovative approaches to the treatment of HF is therefore a top research priority. Although inflammation and immune activation have been implicated in the pathophysiology of HF over the past two decades, the progress for development of new pharmaceutical agents targeting this mechanism was stagnant, especially given that several anti-cytokine clinical trials targeting a single effector cytokine at the peripheral manifestations of HF did not produce clinical benefits. Obviously, the inflammatory mechanisms underlying the pathogenesis of HF have not been challenged. The proposed project studying a role of brain interleukin (IL)-17A (previously known as IL-17) in advancing central inflammation, sympathetic activation and cardiac dysfunction will address the need for a better understanding of the inflammatory mechanisms in HF and provide a novel anti-cytokine approach in treating this devastating disease. The research plan was developed based on the intrinsic property of IL-17A and our compelling preliminary data: 1) IL-17A is a kay inflammatory regulator bridging immune responses and tissue inflammation; 2) It boosts the expression of a broad spectrum of inflammatory mediators in the brain and in the peripheral tissue and cells; 3) Systemic and central administration of IL-17A induced dramatic and long-lasting increases in blood pressure, heart rate and renal sympathetic nerve activity to the levels not seen by other pre-inflammatory cytokines; 4) levels of IL-17A in the plasma, cerebrospinal fluid, and paraventricular nucleus of hypothalamus (PVN, a key cardiovascular and autonomic center of the brain) are higher in a rat model of HF vs. in sham-operated (Sham) animals; and 5) Its receptor, IL-17RA, is highly expressed in the PVN and substantially upregulated in HF. Using a multifaceted approach including electrophysiology, molecular biology, immunocytochemistry, pharmacology, biochemistry and neuroscience in Sham and HF rats, this project will: 1) identify the role of IL-17A in advancing central inflammation in HF; 2) determine the inflammatory mechanisms whereby IL-17A triggers sympathetic activation in HF; 3) evaluate the protective effect of central interventions targeting the IL-17A signaling, alone or in combination with other cytokines in HF. The proposed research will target a master regulator of inflammation rather than a single effector cytokine as a novel anti-cytokine strategy in treating HF, and consider the synergistic actions of multiple cytokines as a potentially more effective means of ameliorating HF. The proposed studies will characterize a previously unrecognized role of brain IL-17A in sympathetic activation and test its potential as a target in treating cardiac dysfunction of HF. Completion of this research project will provide important insights into the anti-inflammation therapeutic strategy in HF and may carry the implication for other cardiovascular disorders like hypertension and metabolic diseases like obesity or diabetes.


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 = $530,606 )
2025	2025	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	5	1/8/2025	NON-COMPETING CONTINUATION	$530,606
														Subtotal = $530,606

Issue Date FY: 2024 ( Subtotal = $577,770 )
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	4	11/29/2023	NON-COMPETING CONTINUATION	$530,606
2024	2024	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	001	4	6/26/2024	NON-COMPETING CONTINUATION	$47,164
														Subtotal = $577,770

Issue Date FY: 2023 ( Subtotal = $589,561 )
2023	2023	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	3	12/12/2022	NON-COMPETING CONTINUATION	$530,606
2023	2023	THE UNIVERSITY OF IOWA	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	001	3	3/6/2023	NON-COMPETING CONTINUATION	$58,955
														Subtotal = $589,561

Issue Date FY: 2022 ( Subtotal = $589,561 )
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	001	2	6/13/2022	NON-COMPETING CONTINUATION	$58,956
2022	2022	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	2	12/20/2021	NON-COMPETING CONTINUATION	$530,605
														Subtotal = $589,561

Issue Date FY: 2021 ( Subtotal = $589,561 )
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	001	1	3/13/2021	NEW	$0
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	000	1	1/8/2021	NEW	$530,606
2021	2021	UNIVERSITY OF IOWA, THE	105 JESSUP HALL	IOWA CITY	IA	52242	JOHNSON	USA	Cardiovascular Diseases Research	002	1	6/12/2021	NEW	$58,955
														Subtotal = $589,561

Grand Total All Awards = $2,877,059

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Novel Role of Interleukin-17 in Sympathetic Activation in Heart Failure

Award Number: R01HL155091

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 01/08/2021

PERIOD OF PERFORMANCE END DATE: 12/31/2025

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