# Protecting the Maternal Heart From Pregnancy-Associated Heart Disease

> **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 2022 · $23,108

## Abstract

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.

## Key facts

- **NIH application ID:** 10438833
- **Project number:** 5R01HD091162-05
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **Principal Investigator:** MICHELLE L MATTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $23,108
- **Award type:** 5
- **Project period:** 2018-08-13 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438833

## Citation

> US National Institutes of Health, RePORTER application 10438833, Protecting the Maternal Heart From Pregnancy-Associated Heart Disease (5R01HD091162-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10438833. Licensed CC0.

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