# Cardiac regeneration by histone deacetylases

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $370,990

## Abstract

Heart disease and heart failure remain the leading causes of morbidity and mortality worldwide. Adult
mammalian heart demonstrates limited regenerative potential. Numerous measures, such as stimulating
preexisting cardiomyocyte proliferation by activating cell cycle, have been attempted previously to induce
heart regeneration, although only modest effects have been achieved to date. Adult cardiomyocytes need to
undergo dedifferentiation first before proliferation, if not simultaneously. In fact, adult zebrafish heart
regeneration is accomplished through both dedifferentiation and proliferation. Chromatin state and
remodeling is often associated with numerous physiological or pathological processes including organ
development, aging, and cancer. However, it is unclear whether epigenetics dictates cardiomyocyte
proliferation capacity, or, whether harnessing epigenetics in adult cardiomyocytes stimulates proliferation.
Through a comparative transcriptomic analysis of murine embryonic day (E) 14.5 hearts (proliferation
active) and adult hearts (proliferation inert), we identified a number of chromatin remodeling factors
including histone deacetylase 7 (HDAC7) that are enriched in E14.5 hearts but missing in adult hearts.
HDAC7 belongs to Class II HDACs, which have specific tissue distributions and shuttle between the
nucleus and cytoplasm in response to signals. Studies have shown that knockout of HDAC7 compromises
vascular integrity during heart development, while overexpression of HDAC7 induces tumor growth and
epithelial proliferation. However, the potential role of HDAC7 in cardiomyocyte proliferation is undetermined.
In our preliminary studies, upon knocking down of HDAC7 in cultured neonatal mouse cardiomyocytes
(NMCMs), we found that cardiomyocyte proliferation was significantly decreased. By contrast,
overexpression of HDAC7 in NMCMs resulted in significant cardiomyocyte dedifferentiation and increased
proliferation. Further, overexpression of HDAC7 in adult cardiomyocytes in vivo significantly induced
cardiomyocyte proliferation and improved cardiac function after myocardial infarction. Based on these novel
and exciting preliminary findings, we hypothesize that HDAC7 is both necessary for cardiomyocyte
proliferation and sufficient to reactivate postnatal cardiomyocyte proliferative and regenerative
potentials. Three aims are proposed to test our central hypothesis. Aim 1: To determine the mechanisms
by which HDAC7 promotes cardiomyocyte proliferation; Aim 2: To determine whether HDAC7 is required for
cardiomyocyte proliferation; Aim 3: To test whether HDAC7 overexpression promotes adult cardiomyocyte
proliferation and improves heart function after myocardial injuries. We intend to achieve these goals by
using a synergistic approach of mouse genetics, developmental and molecular biology, and biochemistry.
Results of these experiments will establish a novel and rigorous therapeutic strategy for promoting heart
regeneration and pave a new path ...

## Key facts

- **NIH application ID:** 10027359
- **Project number:** 1R01HL153406-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Deqiang Li
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,990
- **Award type:** 1
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10027359

## Citation

> US National Institutes of Health, RePORTER application 10027359, Cardiac regeneration by histone deacetylases (1R01HL153406-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10027359. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*