# Unraveling tissue level regulation of thyroid hormone and its role in sex differences in cardiovascular health

> **NIH NIH K01** · UNIVERSITY OF COLORADO DENVER · 2024 · $163,344

## Abstract

PROJECT SUMMARY
Cardiovascular disease (CVD) is the leading global cause of death, claiming approximately 17.9 million lives
annually. Women face a significantly higher risk of heart failure or mortality following a heart attack than men,
yet the molecular mechanisms behind this disparity remain poorly explored. This research aims to determine
the role of thyroid hormones (TH), an underexplored sexually dimorphic risk factor for female heart failure
development, with a primary focus on its tissue-level regulation. TH significantly influences the cardiovascular
system, and the higher prevalence of thyroid disease in women highlights its potential impact on female heart
health. Specifically, the study will concentrate on type 3 deiodinase (DIO3), which regulates TH levels within
tissues. Recent findings from my lab show a sexual dimorphism in Dio3 expression in the heart. We have also
demonstrated that female mice with Dio3 deficiency exhibited compromised cardiac function, including a
reduced ejection fraction, altered mitochondrial substrate utilization, and impaired recovery from myocardial
infarction. These results underscore the protective role of Dio3 in the female heart and the importance of Dio3-
dependent tissue-level TH regulation. This proposal aims to determine the role of Dio3 in cardiovascular health
outcomes in females. The overarching hypothesis is that cardiac Dio3 expression is regulated in a sex-specific
manner, playing a pivotal role in driving sex-specific outcomes in cardiovascular health. In Aim 1, we will
investigate whether Dio3 expression post-MI differs between sexes, potentially contributing to higher heart
failure susceptibility in females. In Aim 2, we will determine the interplay between estrogen and Dio3 in
influencing cardiovascular function in female mice. This aim hypothesizes that low estrogen levels reduce Dio3
activity in female mouse hearts, impairing myocardial function. The study also investigates Dio3's role in
mediating estrogen's cardioprotective effects on cardiovascular function. Together, these aims will address
crucial knowledge gaps regarding thyroid dysfunction and the sexually dimorphic onset of heart failure, aligning
with priorities identified by the NHLBI Working Group. Beyond enhancing our understanding of sex-specific
factors in cardiovascular health, this work will provide vital scientific and technical training to support Dr.
Teixeira's independent program. Ultimately, it will improve women's cardiovascular health, reduce disparities,
and advance cardiovascular science.

## Key facts

- **NIH application ID:** 10947796
- **Project number:** 1K01HL174689-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Silvania da Silva Teixeira
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $163,344
- **Award type:** 1
- **Project period:** 2024-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947796

## Citation

> US National Institutes of Health, RePORTER application 10947796, Unraveling tissue level regulation of thyroid hormone and its role in sex differences in cardiovascular health (1K01HL174689-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10947796. Licensed CC0.

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