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Transcriptomic analysis of left ventricle myocardium in an SHR congenic line with ameliorated cardiac fibrosis

L F Mirchi1, B Chylíková, M Janků

  • 1Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. frantisek.liska@lf1.cuni.cz.

Physiological Research
|August 20, 2019
PubMed

Insights

Researchers identified key genes in a rat model, revealing potential links between circadian rhythms, aldosterone, and hypertension. This discovery offers new insights into metabolic syndrome and its cardiovascular complications.

Area of Science:

  • Cardiovascular Genetics
  • Metabolic Syndrome Research
  • Molecular Biology

Background:

  • Metabolic syndrome and essential hypertension are major global health issues, leading to significant morbidity and mortality primarily through organ damage.
  • Previous studies in a congenic rat line (PD5) showed reduced blood pressure and cardiac fibrosis compared to spontaneously hypertensive rats (SHR).
  • This improvement was linked to a specific segment on chromosome 8 of normotensive polydactylous (PD) origin introgressed into the SHR background.

Purpose of the Study:

  • To investigate the genetic underpinnings of the observed cardioprotective phenotype in the PD5 congenic rat line.
  • To identify differentially expressed genes in the heart tissue of PD5 rats compared to SHR rats.
  • To explore the functional roles of identified genes in the context of metabolic syndrome and hypertension.

Main Methods:

  • Comparative heart transcriptome analysis between SHR and PD5 congenic rats.
  • Bioinformatic analysis of differentially expressed genes using the Database for Annotation, Visualization and Integrated Discovery (DAVID).
  • Validation of protein-level changes for specific genes using Western blotting.

Main Results:

  • Identified 18 differentially expressed genes between SHR and PD5 rat hearts.
  • Four key genes (Per1, Nr4a1, Nr4a3, Kcna5) were associated with circadian rhythm, aldosterone synthesis/secretion, PI3K-Akt signaling, and potassium homeostasis.
  • Confirmed significant upregulation of Nr4a1 at the protein level in PD5 rats.

Conclusions:

  • The genetic modification on chromosome 8 influences cardiac gene expression related to critical physiological pathways.
  • The nuclear receptor subfamily 4 group A member 1 (Nr4a1) is upregulated in the PD5 congenic line and may play a role in the pathogenesis of metabolic syndrome.
  • These findings provide a basis for further research into the molecular mechanisms linking specific genes to hypertension and metabolic disorders.

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