Monday, November 17, 2025 11/17/2025

Vaso-Hormonal Mechanisms in Hypertension

Award Number: P01HL051952
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/1997
PERIOD OF PERFORMANCE END DATE: 03/31/2021

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Vaso-Hormonal Mechanisms in Hypertension - DESCRIPTION (provided by applicant): Increased cardiac Ang II activity from intracellular or interstitial formation (autocrine/paracrine mechanisms) is a cause of cardiac hypertrophic remodeling, arrhythmias, and fibrosis. RAS inhibitors are less effective in blocking Ang II-mediated adverse cardiac remodeling because its production within cardiac myocytes follows non-canonical pathways and the plasma membrane imposes a significant barrier to the external environment. The overarching hypothesis of this Program Project Grant is that the non-canonical pathway for intracellular cardiac Ang II production is mediated by a non-renin/ACE pathway. Cardiac chymase, incorporated into these cells from activated mast cells, acts on an endogenously shorter form of angiotensinogen (Aogen) -angiotensin-(1-12) [Ang-(1-12)] - to generate Ang II. The Project leaders' complementary clinical and basic science expertise in this renewal application will address this concept by examining the intracellular pathways and mechanisms accounting for the chymase-mediated Ang II formation and matrix metalloproteinase activation, the potential role of kallikrein as the Ang-(1-12) generating enzyme from Aogen, and the provocative new finding that estrogen deficiency, by modulating the cardiac intracellular chymase/Ang-(1-12) axis, contributes to the adverse cardiac remodeling and left ventricular diastolic dysfunction in postmenopausal women. The integrated research plan employs genetic models of well characterized altered cardiac function and structure (SHR and congenic mRen2.Lewis hypertensive rats; Projects 1 and 3), a cardiac myocyte cell line (HL-1) that maintains cardiac-specific phenotypes, and human left atrial tissue and cardiac pericardial fluid from subjects undergoing cardiac surgery for the correction of mitral regurgitation (Project 2). The additional novel inclusion of studies in rats expressing the human genes for Aogen, chymase, or both will eventually provide a translational laboratory paradigm for unraveling the cellular and biochemical mechanisms of the distinct biotransformation processes by which the human heart regulates production of Ang II in health and disease. Overall, the combined tightly focused efforts of Drs. Ferrario (Project 1), Dell'Italia (Project 2) and Groban (Project 3) will shed new light on the molecular mechanisms of cardiac Ang II contribution to adverse remodeling and progression to heart failure, the distinct ways by which human and rodent cardiac myocytes differ in terms of the cellular pathways for Ang II production, and how chymase and Ang-(1-12) are regulated by estrogen. These discoveries will identify new therapeutic approaches of higher efficacy when compared to angiotensin converting enzyme inhibitors and Ang II receptor blockers.


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: 2022 ( Subtotal = $574,243 )
2022	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	25	11/3/2021	NON-COMPETING CONTINUATION	$589,314
2022	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	002	25	9/23/2022	NON-COMPETING CONTINUATION	$353
2022	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	25	3/9/2022	NON-COMPETING CONTINUATION	-$15,424
														Subtotal = $574,243

Issue Date FY: 2021 ( Subtotal = -$589,314 )
2021	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	25	8/22/2021	NON-COMPETING CONTINUATION	-$589,314
														Subtotal = -$589,314

Issue Date FY: 2019 ( Subtotal = $1,611,051 )
2019	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	002	25	8/10/2019	NON-COMPETING CONTINUATION	$0
2019	2019	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	25	4/16/2019	NON-COMPETING CONTINUATION	$1,682,622
2019	2018	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	24	12/18/2018	NON-COMPETING CONTINUATION	-$71,571
														Subtotal = $1,611,051

Issue Date FY: 2018 ( Subtotal = $1,804,297 )
2018	2018	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	24	3/23/2018	NON-COMPETING CONTINUATION	$1,768,210
2018	2018	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	24	9/8/2018	NON-COMPETING CONTINUATION	$36,087
														Subtotal = $1,804,297

Issue Date FY: 2017 ( Subtotal = $1,837,581 )
2017	2017	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	23	4/1/2017	NON-COMPETING CONTINUATION	$1,741,868
2017	2017	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	23	8/21/2017	SUPPLEMENT FOR EXPANSION	$95,713
														Subtotal = $1,837,581

Issue Date FY: 2016 ( Subtotal = $1,706,717 )
2016	2016	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	22	3/19/2016	NON-COMPETING CONTINUATION	$1,706,717
														Subtotal = $1,706,717

Issue Date FY: 2015 ( Subtotal = $1,744,692 )
2015	2015	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	21	3/28/2015	COMPETING CONTINUATION	$1,744,692
														Subtotal = $1,744,692

Issue Date FY: 2013 ( Subtotal = $1,716,035 )
2013	2013	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	002	20	7/2/2013	NON-COMPETING CONTINUATION	$95,936
2013	2013	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	20	4/5/2013	NON-COMPETING CONTINUATION	$1,660,467
2013	2012	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	19	4/1/2013	NON-COMPETING CONTINUATION	-$40,368
														Subtotal = $1,716,035

Issue Date FY: 2012 ( Subtotal = $1,954,066 )
2012	2012	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	19	3/28/2012	NON-COMPETING CONTINUATION	$1,954,066
														Subtotal = $1,954,066

Issue Date FY: 2011 ( Subtotal = $1,927,974 )
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	18	6/1/2011	SUPPLEMENT FOR EXPANSION	$69,311
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	18	3/31/2011	NON-COMPETING CONTINUATION	$1,832,439
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	003	18	8/24/2011	SUPPLEMENT FOR EXPANSION	$11,730
2011	2011	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	002	18	8/16/2011	SUPPLEMENT FOR EXPANSION	$14,494
														Subtotal = $1,927,974

Issue Date FY: 2010 ( Subtotal = $1,832,439 )
2010	2010	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	17	3/31/2010	NON-COMPETING CONTINUATION	$1,832,439
														Subtotal = $1,832,439

Issue Date FY: 2009 ( Subtotal = $1,832,439 )
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	002	16	7/24/2009	COMPETING CONTINUATION	$361,293
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	16	5/11/2009	COMPETING CONTINUATION	$0
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	16	4/23/2009	COMPETING CONTINUATION	$1,328,557
2009	2009	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	003	16	8/20/2009	COMPETING CONTINUATION	$142,589
														Subtotal = $1,832,439

Issue Date FY: 2008 ( Subtotal = $2,140,651 )
2008	2008	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	15	3/14/2008	NON-COMPETING CONTINUATION	$2,140,651
														Subtotal = $2,140,651

Issue Date FY: 2007 ( Subtotal = $2,188,465 )
2007	2007	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	14	3/16/2007	NON-COMPETING CONTINUATION	$2,188,465
														Subtotal = $2,188,465

Issue Date FY: 2006 ( Subtotal = $2,203,978 )
2006	2006	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	13	4/4/2006	NON-COMPETING CONTINUATION	$2,203,978
														Subtotal = $2,203,978

Issue Date FY: 2005 ( Subtotal = $2,196,287 )
2005	2005	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	001	12	4/15/2005	SUPPLEMENT FOR EXPANSION	$39,399
2005	2005	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	002	12	8/5/2005	SUPPLEMENT FOR EXPANSION	$28,470
2005	2005	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	12	4/8/2005	NON-COMPETING CONTINUATION	$2,128,418
														Subtotal = $2,196,287

Issue Date FY: 2004 ( Subtotal = $2,063,490 )
2004	2004	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BOULEVARD	WINSTON SALEM	NC	27157	FORSYTH	USA	Cardiovascular Diseases Research	000	11	4/1/2004	COMPETING CONTINUATION	$2,063,490
														Subtotal = $2,063,490

Grand Total All Awards = $37,465,108

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Vaso-Hormonal Mechanisms in Hypertension

Award Number: P01HL051952

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/1997

PERIOD OF PERFORMANCE END DATE: 03/31/2021

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