Myostatin/AKT/FOXO Signaling Is Altered in Human Non-Ischemic Dilated Cardiomyopathy

Lea Hildebrandt1, Maja-Theresa Dieterlen1, Kristin Klaeske1

  • 1Department of Cardiac Surgery, Heart Center, HELIOS Clinic, University Hospital Leipzig, 04289 Leipzig, Germany.

Life (Basel, Switzerland)
|September 23, 2022
PubMed

Insights

The myostatin/AKT/forkhead box O (FOXO) pathway is altered in non-ischemic dilated cardiomyopathy (NIDCM) but not in ischemic dilated cardiomyopathy (IDCM). FOXO1 may be a therapeutic target for NIDCM by regulating muscle atrophy F-box gene (MAFbx) expression.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • Ubiquitin proteasome system disturbances, particularly E3 ligase alterations, are implicated in cardiomyopathy pathogenesis and treatment.
  • The myostatin/AKT/forkhead box O (FOXO) pathway influences E3 ligases, including muscle atrophy F-box gene (MAFbx) and muscle ring-finger protein-1 (MuRF1).

Purpose of the Study:

  • To investigate alterations in the myostatin/AKT/FOXO pathway in ischemic dilated cardiomyopathy (IDCM) and non-ischemic dilated cardiomyopathy (NIDCM).
  • To determine if the expression of myostatin, AKT, FOXO1, FOXO3, MAFbx, and MuRF1 differs between NIDCM, IDCM, and control groups.

Main Methods:

  • Quantification of mRNA and protein expression using real-time polymerase chain reaction and ELISA.
  • Analysis of myocardial tissue from 26 IDCM patients, 23 NIDCM patients, and 17 control subjects (Morrow resection septal tissue).

Main Results:

  • In NIDCM patients, decreased mRNA and protein expression of MAFbx and FOXO1, decreased AKT mRNA, and decreased myostatin protein were observed compared to controls.
  • IDCM patients showed decreased AKT and MAFbx mRNA expression but no other significant differences compared to controls.
  • The myostatin/AKT/FOXO pathway was significantly altered in NIDCM but not in IDCM.

Conclusions:

  • The myostatin/AKT/FOXO pathway is dysregulated in non-ischemic dilated cardiomyopathy.
  • FOXO1 emerges as a potential therapeutic target for managing MAFbx expression in NIDCM.

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