# Supply and Demand: Oxygen and Workload Regulate Cardiomyocyte Proliferation

> **NIH NIH R35** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $1,034,446

## Abstract

Heart failure is a devastating disease with mortality rates exceeding many malignancies.
The pathophysiological basis of systolic heart failure lies in the inability of the adult
mammalian heart to regenerate lost or damaged myocardium. Although limited
cardiomyocyte turnover does in fact occur in the adult mammalian heart, it is insufficient
for restoration of contractile function following injury. In contrast to the adult mammalian
heart, my group has shown that newborn mammals have a remarkable endogenous
myocardial regenerative capacity, mediated by proliferation of preexisting
cardiomyocytes. Nevertheless, the mere realization that the heart is not a post-mitotic
organ created a lot of excitement in the past two decades and led to a flurry of bench and
clinical studies aimed at outlining the cardiac regenerative potential of various cell types.
While many of these studies may hold therapeutic promise, mounting evidence suggest
that cell therapy may enhance some endogenous repair or regenerative mechanisms such
as stimulation of cardiomyocyte proliferation. Importantly, current evidence suggests that
both the regenerative ability of the early postnatal heart, and cardiomyocyte turnover in
the adult heart are mediated by proliferative competency of pre-existing cardiomyocytes.
However, mechanisms of regulation of mammalian cardiomyocyte cell cycle arrest shortly
after birth remain poorly understood. Therefore, we believe that a program focused on
understanding mechanisms of cardiomyocyte cell cycle regulation could inform future
therapeutic interventions for heart regeneration. Our studies are focused on three broad
questions: 1) Is loss of the regenerative capacity of the mammalian myocardium an
evolutionary tradeoff to gain metabolic efficiency? 2) How is the slow turnover of
cardiomyocytes in the adult heart regulated? 3) Does cardiac mechanical load represent
a regenerative block

## Key facts

- **NIH application ID:** 10774267
- **Project number:** 5R35HL166563-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Hesham Sadek
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,034,446
- **Award type:** 5
- **Project period:** 2023-02-15 → 2030-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10774267

## Citation

> US National Institutes of Health, RePORTER application 10774267, Supply and Demand: Oxygen and Workload Regulate Cardiomyocyte Proliferation (5R35HL166563-02). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10774267. Licensed CC0.

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