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Differential cardiomyocyte transcriptomic remodeling during in vitro Trypanosoma cruzi infection using laboratory

Katherine-Sofia Candray-Medina1,2,3, Yu Nakagama4,5, Masamichi Ito6,7

  • 1Department of Parasitology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan.

Tropical Medicine and Health
|December 8, 2023
PubMed

Insights

Different Trypanosoma cruzi strains impact cardiomyocyte gene expression, leading to oxidative stress and hypertrophy. This study reveals distinct transcriptomic signatures associated with Chagas cardiomyopathy progression.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Parasitology

Background:

  • Chagas disease causes life-threatening cardiac issues.
  • Genetic variations in Trypanosoma cruzi (T. cruzi) strains may influence disease severity and Chagas cardiomyopathy (CCM) progression.

Purpose of the Study:

  • To investigate the transcriptomic differences in cardiomyocytes infected with distinct T. cruzi strains.
  • To explore the link between these transcriptomic changes and CCM pathogenesis.

Main Methods:

  • HL-1 cardiomyocytes were infected with Colombian, Y, or Tulahuen T. cruzi strains.
  • Microarray analysis was performed on RNA isolated post-infection.
  • Gene expression, biological pathways, and intracellular reactive oxygen species (ROS) levels were analyzed.

Main Results:

  • Upregulation of oxidative stress, hypertrophy, apoptosis, and MAPK signaling pathways was observed.
  • Colombian/Y strains uniquely upregulated glutathione/one-carbon metabolism and nitrogen metabolism pathways.
  • T. cruzi infection significantly increased intracellular ROS levels in cardiomyocytes.

Conclusions:

  • Oxidative stress and hypertrophic pathways are universal responses to T. cruzi infection in cardiomyocytes.
  • Nitrogen and glutathione metabolism alterations may link nitrosative stress and impaired radical scavenging to CCM pathophysiology.
Abstract

Keywords:
Chagas diseaseDilated cardiomyopathyGlutathione metabolismHL-1In vitro modelingNeglected tropical diseasesOxidative stressTranscriptomeTrypanosoma cruzi

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