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

Physiol Res. 2019 Oct 25;68(5):747-755. doi: 10.33549/physiolres.934127. Epub 2019 Aug 19.

Abstract

Metabolic syndrome and one of its manifestations, essential hypertension, is an important cause of worldwide morbidity and mortality. Morbidity and mortality associated with hypertension are caused by organ complications. Previously we revealed a decrease of blood pressure and an amelioration of cardiac fibrosis in a congenic line of spontaneously hypertensive rats (SHR), in which a short segment of chromosome 8 (encompassing only 7 genes) was exchanged for a segment of normotensive polydactylous (PD) origin. To unravel the genetic background of this phenotype we compared heart transcriptomes between SHR rat males and this chromosome 8 minimal congenic line (PD5). We found 18 differentially expressed genes, which were further analyzed using annotations from Database for Annotation, Visualization and Integrated Discovery (DAVID). Four of the differentially expressed genes (Per1, Nr4a1, Nr4a3, Kcna5) belong to circadian rhythm pathways, aldosterone synthesis and secretion, PI3K-Akt signaling pathway and potassium homeostasis. We were also able to confirm Nr4a1 2.8x-fold upregulation in PD5 on protein level using Western blotting, thus suggesting a possible role of Nr4a1 in pathogenesis of the metabolic syndrome.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Animals, Congenic
  • Blood Pressure / genetics
  • Cardiomyopathies / genetics*
  • Cardiomyopathies / metabolism
  • Cardiomyopathies / pathology
  • Disease Models, Animal
  • Fibrosis
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Heart Ventricles / metabolism*
  • Heart Ventricles / pathology
  • Hypertension / genetics*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Male
  • Metabolic Syndrome / genetics*
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / physiopathology
  • Phenotype
  • Rats, Inbred SHR
  • Signal Transduction / genetics
  • Transcriptome*
  • Ventricular Function, Left / genetics*
  • Ventricular Remodeling / genetics*