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Long-Term Transcriptomic Changes and Cardiomyocyte Hyperpolyploidy after Lactose Intolerance in Neonatal Rats.

Olga V Anatskaya1, Andrey L Runov2,3, Sergey V Ponomartsev1

  • 1Institute of Cytology RAS, Saint Petersburg 194064, Russia.

International Journal of Molecular Sciences
|April 28, 2023
PubMed
Summary
This summary is machine-generated.

Neonatal lactose intolerance (NLI) causes long-term growth retardation and cardiac inflammation in rats. This inflammation permanently alters heart cell gene expression, potentially leading to adult cardiovascular disease.

Keywords:
DNA instabilitycardiomyocytedevelopmental programming of adult heart diseasesfibrosisglutathione deficiencyinflammationneonatal lactose intolerancepolyploidyqualitative transcriptome analysisthyroid deficiency

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Area of Science:

  • Cardiovascular Science
  • Developmental Biology
  • Molecular Biology

Background:

  • Cardiovascular diseases can stem from early life growth issues.
  • The precise mechanisms linking neonatal development to adult heart health are not fully understood.

Purpose of the Study:

  • To investigate if systemic inflammation from neonatal lactose intolerance (NLI) impacts cardiac development and cardiomyocyte gene regulation long-term.
  • To test the hypothesis that NLI triggers lasting pathological changes in heart development.

Main Methods:

  • Utilized a rat model of NLI induced by lactose overload.
  • Employed cytophotometry, image analysis, and mRNA sequencing (mRNA-seq).
  • Evaluated cardiomyocyte ploidy, DNA damage, and transcriptomic alterations.

Main Results:

  • NLI led to sustained growth retardation and cardiomyocyte hyperpolyploidy in rats.
  • Observed significant transcriptomic changes associated with heart pathologies like inflammation, fibrosis, and DNA instability.
  • Identified impaired thyroid hormone, calcium, and glutathione signaling as potential causes.
  • Found gene expression patterns linked to increased cardiomyocyte polyploidy and open chromatin.

Conclusions:

  • Neonatal inflammation due to NLI can permanently alter cardiac gene regulatory networks and cardiomyocyte transcriptome.
  • These ploidy-related epigenetic changes acquired neonatally may predispose to adult cardiovascular disease.
  • NLI is a potential trigger for developmental programming of adult heart conditions, suggesting avenues for preventive strategies.