Depressed expression of MuRF1 and MAFbx in areas remote of recent myocardial infarction: a mechanism contributing to myocardial remodeling?

Basic Res Cardiol. 2010 Mar;105(2):219-26. doi: 10.1007/s00395-009-0068-5. Epub 2009 Oct 27.

Abstract

Ventricular remodeling following myocardial infarction (MI) includes myocardial hypertrophy, a process requiring increased protein synthesis and sarcomere assembly. The anti-hypertrophic effect of MuRF1/MafBx, both muscle-specific E3-ubiquitin ligases, has been demonstrated in animal experiments and in cultured cardiomyocytes. We assessed MuRF1/MAFbx expression in myocardium remote of recently (<2 weeks) infarcted regions (MI), compared with patients undergoing coronary artery bypass surgery, with normal systolic function and without previous infarction (control or Con). Left ventricular myocardial biopsies were obtained from the contralateral normal zone in MI (n = 14) patients and from the Con (n = 12) group. MuRF-1/MAFbx expression was assessed using RT-PCR and Western blot (WB). In addition, the myocardial expression of TNF-alpha was measured (RT-PCR) and troponin I, beta-myosin and phosphorylated Akt/Akt (pAkt/Akt) were quantified (WB). MuRF1 and MAFbx expression (mRNA and protein level) were significantly reduced in biopsies from MI patients. TNF-alpha was significantly higher in MI and exhibited a negative correlation with MuRF1 and MAFbx. The expression of troponin I and cardiomyocyte size were increased in MI in comparison to Con, whereas beta-myosin expression was not altered. When compared with Con, pAkt/Akt was elevated. The results of the present study suggest that the atrogenes MuRF1/MAFbx are involved in regulating the hypertrophic response, characteristic of the early post-infarction remodeling phase. Reduced expression of MuRF1 and MAFbx in the myocardium might permit hypertrophy, which is supported by the elevation of troponin I. A regulatory role of TNF-alpha needs to be confirmed in further experiments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biopsy
  • Coronary Artery Disease / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle Proteins / metabolism*
  • Myocardial Infarction / metabolism*
  • Myocardial Infarction / pathology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Myocytes, Cardiac / pathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger / metabolism
  • SKP Cullin F-Box Protein Ligases / metabolism*
  • Signal Transduction
  • Tripartite Motif Proteins
  • Troponin I / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Ubiquitin-Protein Ligases / metabolism*
  • Ventricular Myosins / metabolism
  • Ventricular Remodeling*

Substances

  • Muscle Proteins
  • RNA, Messenger
  • Tripartite Motif Proteins
  • Troponin I
  • Tumor Necrosis Factor-alpha
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • TRIM63 protein, human
  • Ubiquitin-Protein Ligases
  • Proto-Oncogene Proteins c-akt
  • Ventricular Myosins