Patterns of desmin expression in idiopathic dilated cardiomyopathy are related to the desmin mRNA and ubiquitin expression

J Investig Med. 2019 Jan;67(1):11-19. doi: 10.1136/jim-2017-000707. Epub 2018 Aug 10.

Abstract

Desmin expression depends on desmin messenger RNA (mRNA) and ubiquitin proteasome system. This process is poorly understood in dilated cardiomyopathy. The aim of the study was to investigate whether changes of desmin mRNA and ubiquitin expression correlate with types of desmin expression in cardiomyocytes. Endomyocardial biopsy was performed in 60 patients (85% men, mean age 46±14 years) with heart failure (HF; left ventricular ejection fraction <45%). Desmin and ubiquitin expression were analysed in histological sections by immunohistochemistry and in Western blot. Desmin mRNA expression was determined by fluorescent in situ hybridization methods. In patients with weak/even desmin expression, weak/even expression of ubiquitin in the cytosol and low desmin mRNA expression in the cytosol and nuclei of cardiomyocytes were observed. Expression of ubiquitin and desmin mRNA increased along with the progression of desmin cytoskeleton remodeling. Desmin mRNA and ubiquitin were weakly expressed/absent in cardiomyocytes with low/lack of desmin expression. Variations in desmin mRNA, desmin and ubiquitin expression were associated with gradual changes in myocardial structure and clinical parameters. To conclude, changes in ubiquitin and desmin mRNA expression are related to patterns of desmin expression. An increase in the expression of ubiquitin and desmin mRNA may be a protective feature against unfavorable cell remodeling. This may reduce the adverse effects of cytoskeleton damage in the early stages of HF. Low/lack ubiquitin and/or desmin mRNA expression may be markers of end-stage HF.

Keywords: cardiomyopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiomyopathy, Dilated / diagnostic imaging
  • Cardiomyopathy, Dilated / genetics*
  • Cardiomyopathy, Dilated / pathology
  • Desmin / genetics*
  • Desmin / metabolism
  • Female
  • Fibrosis
  • Gene Expression Regulation*
  • Humans
  • Male
  • Middle Aged
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Natriuretic Peptide, Brain / metabolism
  • Peptide Fragments / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ubiquitin / genetics*
  • Ubiquitin / metabolism

Substances

  • Desmin
  • Peptide Fragments
  • RNA, Messenger
  • Ubiquitin
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain