# Elucidating the endocrine regulation of cardiac regeneration in vertebrates

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $37,186

## Abstract

ABSTRACT
Organ regenerative potential varies ontologically and phylogenetically. While lower vertebrates and
neonatal mammals retain robust capacities for heart regeneration, adult mammals generally resolve
cardiac injury through fibrosis, not regeneration. However, the underlying mechanisms driving loss of
such a seemingly advantageous trait in evolution and development remain enigmatic. Mammalian hearts
lose regenerative potential due to cardiomyocyte cell-cycle withdrawal and polyploidization. Using
cardiomyocyte ploidy as an indicator of regenerative potential, we screened 23 mammalian species and
identified the Naked-Mole Rat (NMR), Heterocephalus glaber, as having an unusually high diploid
cardiomyocyte percentage. We uncovered a robust correlation between cardiomyocyte ploidy and
standard metabolism, a physiological parameter primarily regulated by thyroid hormone (TH). Serum
TH in NMRs is unusually low for a mammal, and preliminary evidence suggests NMR cardiomyocytes
can proliferate. Additionally, we have observed that TH inhibition enhances mouse cardiomyocyte
proliferation and reduces ploidy, while exogenous TH inhibits cardiomyocyte proliferation in zebrafish.
Thus, we hypothesize that NMRs possess enhanced cardiac regenerative potential and that the distinct
TH levels in NMRs, mice, and zebrafish contribute to their distinct cardiac regenerative
potentials. Our Aim #1 will assess NMR cardiac regenerative potential in vitro and in vivo. Aim
#2 will determine if TH inhibition enhances cardiac regeneration in adult mice. Aim #3 will test whether
exogenous TH inhibits cardiac regeneration in zebrafish. Studying the influence of TH over cardiac
regeneration could yield novel insights into the molecular control of organ regenerative potential in
development and evolution.

## Key facts

- **NIH application ID:** 9970162
- **Project number:** 5F31HL145935-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Stephen Cutie
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $37,186
- **Award type:** 5
- **Project period:** 2019-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970162

## Citation

> US National Institutes of Health, RePORTER application 9970162, Elucidating the endocrine regulation of cardiac regeneration in vertebrates (5F31HL145935-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9970162. Licensed CC0.

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