Skip to main content
NUTRITION 2024 Main banner
Icon Legend
This session is not in your schedule.
This session is in your schedule. Click again to remove it.
Back

Energy and Macronutrient Metabolism (Poster Session)

(P06-008-24) O-GlcNAcylation Regulates Postnatal Heart Regeneration After Myocardial Infarction

Sunday, June 30, 2024
12:45 PM – 1:45 PM CT
Location: Poster Board 256
Disclosure(s):
Jongbeom Jin: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Heart failure is a leading cause of mortality in the United States, with poor heart regeneration following injury, such as infarction, being a significant contributor to systolic heart failure in adult mammals. We have previously demonstrated that neonatal mice have the ability to regenerate their hearts after injury, a capability that is lost seven days after birth. This loss coincides with a critical shift in cardiomyocyte energy metabolism during the transition from neonatal to adult stages. O-GlcNAcylation (O‐GlcNAc), a common modification on nuclear and cytoplasmic proteins, is crucial for regulating glucose metabolism and increases with elevated glucose uptake. O-GlcNAc levels, regulated by the enzymes O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), are essential for cellular functions, including signal transduction, transcription, and translation. Inhibiting OGA enhances O-GlcNAcylation levels. However, the effects of OGA inhibition on heart failure and regeneration in mouse models have not been fully studied.

Methods: We hypothesize that OGA inhibition by NButGT injection will promote cardiomyocyte proliferation and heart regeneration. To investigate the role of OGA inhibition in heart regeneration, we utilized neonatal mice at postnatal day 7 (P7) for myocardial infarction (MI) surgery. The mice were treated with the OGA inhibitor NButGT for ten days before and after the MI injury. We performed various analyses, including immunohistochemistry to measure cardiomyocyte proliferation and trichrome staining to evaluate heart regeneration.

Results: Our results show that inhibiting OGA by NButGT injection after MI promotes cardiomyocyte proliferation, as indicated by the mitosis marker phospho-histone 3 (pH3) staining. Remarkably, NButGT injection to the neonatal mouse heart for ten days before and after MI injury reduces scar formation and promotes heart regeneration, as revealed by trichrome staining.

Conclusions: OGA inhibition by NButGT promotes postnatal cardiomyocyte proliferation and heart regeneration. These findings suggest a promising new therapeutic strategy for treating human heart failure.

Funding Sources: OSU Start-up, OSU One Health, OCASCR Research grants to J.B.