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Senescence dysregulates of inflammation-resolution programs in atherosclerosis

Award Number: R01HL153019
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/15/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Senescence dysregulates of inflammation-resolution programs in atherosclerosis - Atherosclerotic cardiovascular disease (CVD) is the leading cause of death in the industrialized world. Failed resolution of a chronic inflammatory response is an important driving force in the progression of atherosclerosis. Resolution is mediated by the critical balance between specialized pro-resolving mediators (SPMs) such as lipoxins and resolvins and pro-inflammatory factors like leukotrienes (LTs) and prostaglandins (PGs). Previous work from our lab and others suggest that SPMs are defectively synthesized in plaques and that restoration of SPMs prevents atherosclerosis progression in mice. Gaps remain in our understanding as to a) what cellular processes derange the synthesis of SPMs in protective actions of SPMs in atherosclerosis. Therefore, the plaques and b) mechanisms associated with the overall objective of this proposal is to understand new mechanisms of dysregulated resolution in atherosclerosis and to harness new SPM signaling pathways towards a novel treatment strategy. Cellular senescence is an irreversible cell cycle arrest that leads to a highly pro-inflammatory phenotype called the senescence-associated secretory phenotype (SASP). Prominent features of senescent cells (SCs) include elevated levels of COX2 and PGs and heightened glycolysis. SCs recently emerged as a driver of plaque necrosis but mechanisms are poorly understood. Our new work suggests that senescence impairs endogenous resolution programs and that key SPMs can limit the SASP. We proposed a series of studies to identify the mechanisms associated with senescence and impaired resolution (Aim I), the link between myeloid senescent cells and SPM formation in plaques (Aim II) and mechanisms underlying how hypercholesterolemia impacts senescence and SPM synthesis (Aim III). The link between dysregulated resolution programs and senescence is a completely new and unexplored area of research that may reveal new treatment strategies for atherosclerosis that are complementary to those that currently exist.


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 = -$25,414 )
2026	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	000	4	12/18/2025	NON-COMPETING CONTINUATION	-$25,414
														Subtotal = -$25,414

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE # A34	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	000	4	7/11/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $669,977 )
2023	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	000	4	6/2/2023	NON-COMPETING CONTINUATION	$617,817
2023	2023	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	001	4	6/3/2023	SUPPLEMENT FOR EXPANSION	$52,160
														Subtotal = $669,977

Issue Date FY: 2022 ( Subtotal = $669,977 )
2022	2022	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	001	3	6/3/2022	SUPPLEMENT FOR EXPANSION	$52,160
2022	2022	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	000	3	5/31/2022	NON-COMPETING CONTINUATION	$617,817
														Subtotal = $669,977

Issue Date FY: 2021 ( Subtotal = $666,174 )
2021	2021	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	001	2	8/20/2021	SUPPLEMENT FOR EXPANSION	$48,357
2021	2021	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	000	2	6/11/2021	NON-COMPETING CONTINUATION	$617,817
														Subtotal = $666,174

Issue Date FY: 2020 ( Subtotal = $642,668 )
2020	2020	ALBANY MEDICAL COLLEGE	47 NEW SCOTLAND AVE	ALBANY	NY	12208	ALBANY	USA	Cardiovascular Diseases Research	000	1	7/10/2020	NEW	$642,668
														Subtotal = $642,668

Grand Total All Awards = $2,623,382

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Senescence dysregulates of inflammation-resolution programs in atherosclerosis

Award Number: R01HL153019

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/15/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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