# Genetic Analysis of Cardiac Growth

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $441,250

## Abstract

Abstract
 In mammals, fetal cardiac myocytes (CMs) proliferate robustly, contributing to the growth of the heart in
utero. Postnatally, cell cycle genes are dramatically down-regulated and the ability of CMs to enter the cell
cycle is lost after postnatal day 7. The lack of cell cycle gene expression in adult CMs (ACMs) suggests these
genes are stably silenced and no longer able to respond to growth stimuli. As a result of this very limited
proliferative potential, the mammalian heart has long been thought of as a non-regenerative organ. This has
been challenged by increasing evidence demonstrating that postnatal CMs do proliferate and contribute to
myocardial renewal but at a very low rate. The lack of cell cycle gene expression in ACMs is reminiscent of
other biologic processes such as senescence or cell cycle checkpoints where epigenetic mechanisms stably
silence gene transcription through the formation of heterochromatin. This proposal hypothesizes that cell cycle
genes are stably silenced in ACMs through a highly regulated process that involves trimethylation of histone
H3 on lysine 9 (H3K9me3), which then recruits the epigenetic machinery at cell cycle promoters leading to
stable gene silencing. The corollary of this model, if true, is that manipulating this epigenetic process and the
proteins that mediate heterochromatin formation could promote cell cycle re-entry in ACMs, a first step towards
cardiac proliferation and myocardial regeneration.
PHS 398/2590 (Rev. 11/07) Page Continuation Format Page

## Key facts

- **NIH application ID:** 9838764
- **Project number:** 5R01HL070748-12
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** William Robb MacLellan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $441,250
- **Award type:** 5
- **Project period:** 2004-04-05 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9838764

## Citation

> US National Institutes of Health, RePORTER application 9838764, Genetic Analysis of Cardiac Growth (5R01HL070748-12). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9838764. Licensed CC0.

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