# Project 3 - Role of Proline Metabolism in Regulation of Mammalian Cardiomyocyte Proliferation

> **NIH NIH P01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $430,009

## Abstract

ABSTRACT
 (Project 3)
Role of Proline Metabolism in Regulation of Mammalian Cardiomyocyte Proliferation
Heart failure progression is a complex biological process that is precipitated by the maladaptive myocardial
response to injury, compounded by failure of the adult heart to replace lost or damaged cardiomyocytes. Our lab
has previously outlined the regenerative capacity of the newborn mammalian heart and outlined several
mechanisms that regulate this process. Specifically, we demonstrate that the endogenous regenerative capacity
of the newborn heart is mediated by proliferation of preexisting cardiomyocytes and is lost when cardiomyocytes
exit cell cycle within a few days after birth. We described several fundamental mechanisms that regulate cell
cycle exit of cardiomyocytes, including spontaneous DNA damage that occurs as a result of increased
mitochondrial oxidative phosphorylation. Subsequently, we demonstrated that gradual severe systemic hypoxia
can induce cardiomyocyte proliferation in the adult mouse heart and is associated with decreased DNA damage.
These finding suggest that oxygen metabolism is an upstream signal that mediates postnatal cardiomyocyte cell
cycle in the postnatal heart. Intriguingly, we found that proline metabolism was markedly upregulated in
regenerative cardiomyocytes under hypoxic conditions. From a mechanistic standpoint, we want to better
understand the factors that regulate cardiomyocyte proliferation under hypoxia. Therefore, this proposal will
examine the role of proline metabolism in regulation of cardiomyocyte adaptation and proliferation under hypoxia
in both mice and pigs. In addition, we will examine the role of Hypoxia inducible factors (Hifs) in regulation of
proline metabolism and cardiomyocyte proliferation in the neonatal heart and under hypoxic conditions.

## Key facts

- **NIH application ID:** 10677735
- **Project number:** 5P01HL160476-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Hesham Sadek
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $430,009
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10677735

## Citation

> US National Institutes of Health, RePORTER application 10677735, Project 3 - Role of Proline Metabolism in Regulation of Mammalian Cardiomyocyte Proliferation (5P01HL160476-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10677735. Licensed CC0.

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