Wednesday, December 4, 2024 12/4/2024

Reactive Species in Vascular Disease: Mechanisms of Injury

Award Number: R01HL054926
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract While the molecular mechanisms for the regulation of vascular tone by nitric oxide are well appreciated, the targets of nitric oxide (NO) signaling at the proteome level are incomplete. Decline in synthesis and bioavailability of NO is central to the pathogenesis of cardiovascular diseases and in age-dependent deterioration of vascular function and cardiac muscle performance. However, the signaling pathways affected by the decline in bioavailable NO during ageing remain unclear. Furthermore, several current clinical trials aim to restore the levels of NO in humans with hopes to improve cardiovascular and skeletal muscle physiological function and prevent vascular disease and disability in aged populations. Presently, the signaling pathways reestablished by pharmacological restoration of NO remain unknown. Therefore, we propose to use chemoselective, high- resolution, mass spectrometry-based proteomic technologies to identify and quantify for the first time at the organ and cellular level the two post-translational modifications protein phosphorylation and cysteine S-nitrosation, that constitute the two principle NO signaling pathways. We will resolve changes in the canonical signaling cascade, activation of soluble guanylate cyclase, production of cGMP and Ser/Thr phosphorylation of proteins and the complimentary selective S-nitrosylation of cysteine residues as a function of gender, ageing and in the setting of NO deficiency before and after restoration of bioavailable NO. Guided by preliminary data we will also investigate a novel mechanism for the regulation of the NAD-dependent protein deacetylase sirtuin 2 by NO. This regulatory function may have important cardioprotective functions. Completion of the proposed aims will provide new mechanistic insights and a framework for system-level appreciation of NO signalling in the cardiovascular system.


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 = $0 )
2025	2023	THE CHILDREN'S HOSPITAL OF PHILADELPHIA	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	24	10/24/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $440,000 )
2023	2023	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	24	11/30/2022	NON-COMPETING CONTINUATION	$396,000
2023	2023	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	24	2/11/2023	NON-COMPETING CONTINUATION	$44,000
														Subtotal = $440,000

Issue Date FY: 2022 ( Subtotal = $440,000 )
2022	2022	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	23	6/18/2022	NON-COMPETING CONTINUATION	$44,000
2022	2022	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	23	11/9/2021	NON-COMPETING CONTINUATION	$396,000
														Subtotal = $440,000

Issue Date FY: 2021 ( Subtotal = $440,000 )
2021	2021	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	22	11/17/2020	NON-COMPETING CONTINUATION	$396,000
2021	2021	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	002	22	5/14/2021	NON-COMPETING CONTINUATION	$44,000
2021	2020	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	21	10/27/2020	COMPETING CONTINUATION	$0
														Subtotal = $440,000

Issue Date FY: 2020 ( Subtotal = $440,000 )
2020	2020	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	21	11/29/2019	COMPETING CONTINUATION	$440,000
2020	2018	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	20	3/12/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $440,000

Issue Date FY: 2018 ( Subtotal = $420,000 )
2018	2018	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	20	5/4/2018	NON-COMPETING CONTINUATION	$420,000
														Subtotal = $420,000

Issue Date FY: 2017 ( Subtotal = $420,000 )
2017	2017	CHILDREN'S HOSPITAL OF PHILADELPHIA, THE	3401 CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	19	4/14/2017	NON-COMPETING CONTINUATION	$420,000
														Subtotal = $420,000

Issue Date FY: 2016 ( Subtotal = $420,000 )
2016	2016	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	18	4/1/2016	NON-COMPETING CONTINUATION	$420,000
														Subtotal = $420,000

Issue Date FY: 2015 ( Subtotal = $420,000 )
2015	2015	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	17	6/29/2015	COMPETING CONTINUATION	$420,000
2015	2014	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	16	6/29/2015	NON-COMPETING CONTINUATION	$0
														Subtotal = $420,000

Issue Date FY: 2014 ( Subtotal = $410,375 )
2014	2014	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	16	3/4/2014	NON-COMPETING CONTINUATION	$410,375
														Subtotal = $410,375

Issue Date FY: 2013 ( Subtotal = $398,650 )
2013	2013	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	15	4/2/2013	NON-COMPETING CONTINUATION	$376,875
2013	2013	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	001	15	6/26/2013	NON-COMPETING CONTINUATION	$21,775
														Subtotal = $398,650

Issue Date FY: 2012 ( Subtotal = $418,750 )
2012	2012	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	14	3/8/2012	NON-COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2011 ( Subtotal = $418,750 )
2011	2011	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	13	7/14/2011	COMPETING CONTINUATION	$418,750
														Subtotal = $418,750

Issue Date FY: 2009 ( Subtotal = $319,459 )
2009	2009	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	12	6/24/2009	NON-COMPETING CONTINUATION	$319,459
														Subtotal = $319,459

Issue Date FY: 2008 ( Subtotal = $319,459 )
2008	2008	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	11	6/19/2008	NON-COMPETING CONTINUATION	$319,459
														Subtotal = $319,459

Issue Date FY: 2007 ( Subtotal = $320,430 )
2007	2007	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	10	6/20/2007	NON-COMPETING CONTINUATION	$320,430
														Subtotal = $320,430

Issue Date FY: 2006 ( Subtotal = $330,000 )
2006	2006	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	9	7/24/2006	COMPETING CONTINUATION	$330,000
														Subtotal = $330,000

Issue Date FY: 2005 ( Subtotal = $340,000 )
2005	2005	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	8	3/8/2005	NON-COMPETING CONTINUATION	$340,000
														Subtotal = $340,000

Issue Date FY: 2004 ( Subtotal = $340,000 )
2004	2004	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	7	2/12/2004	NON-COMPETING CONTINUATION	$340,000
														Subtotal = $340,000

Issue Date FY: 2003 ( Subtotal = $340,000 )
2003	2003	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	6		NON-COMPETING CONTINUATION	$340,000
														Subtotal = $340,000

Issue Date FY: 2002 ( Subtotal = $340,000 )
2002	2002	CHILDREN'S HOSPITAL OF PHILADELPHIA	34TH ST & CIVIC CENTER BLVD	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Cardiovascular Diseases Research	000	5	3/22/2002	COMPETING CONTINUATION	$340,000
														Subtotal = $340,000

Issue Date FY: 1999 ( Subtotal = $128,979 ) (Continued on the next page)
Grand Total All Awards = $7,990,107

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Reactive Species in Vascular Disease: Mechanisms of Injury

Award Number: R01HL054926

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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