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Protecting the maternal heart from pregnancy associated heart disease

Award Number: R01HD091162
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/13/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Protecting the maternal heart from pregnancy associated heart disease - Project Summary Postpartum cardiomyopathy (PPCM) is a disease of unknown etiology that arises as a complication of pregnancy in women with no prior heart disease. It occurs in 1:1800 to 1:3500 births in the United States and is characterized by an acute onset of heart failure during the last month of pregnancy or within five months postpartum. PPCM is a major cause of maternal morbidity and mortality with no PPCM-specific treatment options available. During pregnancy, pregnancy-associated hypertrophy initiates the activation of cardiomyocyte protective signaling pathways that block stress-mediated apoptosis. In PPCM patients there is an increase in cardiomyocyte apoptosis that leads to irreversible dysfunction and heart failure. The cellular mechanisms driving cardiomyocyte apoptosis are not fully understood. We have identified a gene PTRH2 (also called Bit-1) that is evolutionarily conserved, mediates integrin regulated cell survival and apoptosis, and mutations in this gene promote multisystem disease in humans. We hypothesize that PTRH2 is essential for cardioprotection from peripartum stresses in the maternal heart. To study this we developed a cardiomyocyte-specific deletion of PTRH2 (CKO). CKO male and never- pregnant female mice demonstrate no heart defects and live to old age. However, 100% of CKO pregnant female mice develop PPCM in a dose-dependent manner (CKO>HET). We will use cell and molecular biology and our CKO mice to determine how PTRH2 mediates cardioprotection, test whether PTRH2 associated proteins abrogate the PPCM phenotype in CKO pregnant mice, determine whether PTRH2 expression blocks hypertrophy and examine PPCM patient heart samples for PTRH2 gene mutations. The proposed project has the potential to identify an essential survival pathway that is activated in pregnancy-associated hypertrophy, test PTRH2 directed therapeutic strategies in a preclinical mouse model of PPCM and determine whether mutations in PTRH2 promote PPCM.


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 = -$7,395 )
2026	2022	THE ADMINISTRATORS OF TULANE EDUCATIONAL FUND	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Child Health and Human Development Extramural Research	000	6	12/15/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$7,395
														Subtotal = -$7,395

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Child Health and Human Development Extramural Research	000	6	7/15/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = -$32,975 )
2023	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	000	5	3/10/2023	NON-COMPETING CONTINUATION	-$361,892
2023	2022	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	003	5	5/15/2023	NON-COMPETING CONTINUATION	-$23,108
2023	2022	ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, THE	6823 SAINT CHARLES AVE	NEW ORLEANS	LA	70118	ORLEANS	USA	Child Health and Human Development Extramural Research	001	6	3/13/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$357,192
2023	2021	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	004	4	6/20/2023	NON-COMPETING CONTINUATION	-$1,430
2023	2021	UNIVERSITY OF HAWAII	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	002	4	5/15/2023	NON-COMPETING CONTINUATION	-$3,736
														Subtotal = -$32,975

Issue Date FY: 2022 ( Subtotal = $385,000 )
2022	2022	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	000	5	7/4/2022	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2021 ( Subtotal = $385,000 )
2021	2021	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	000	4	6/25/2021	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2020 ( Subtotal = $385,000 )
2020	2020	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	000	3	6/15/2020	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2019 ( Subtotal = $385,000 )
2019	2019	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	000	2	5/31/2019	NON-COMPETING CONTINUATION	$385,000
														Subtotal = $385,000

Issue Date FY: 2018 ( Subtotal = $385,000 )
2018	2018	UNIVERSITY OF HAWAII SYSTEMS	2425 CAMPUS RD SINCLAIR RM 1	HONOLULU	HI	96822	HONOLULU	USA	Child Health and Human Development Extramural Research	000	1	8/10/2018	NEW	$385,000
														Subtotal = $385,000

Grand Total All Awards = $1,884,630

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Protecting the maternal heart from pregnancy associated heart disease

Award Number: R01HD091162

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 03/13/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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