Abstract 3866: Depressed Expression of MuRF1 And MafBx in Areas Remote of Recent Myocardial Infarction
Aims: Ventricular remodelling 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 to patients undergoing coronary artery bypass surgery, with normal systolic function and without previous infarction (Control or C).
Methods: Left ventricular myocardial biopsies were obtained from the contralateral normal zone in MI (n=14) patients and from the C (n=12) group. MuRF-1/MAFbx expression was assessed using RT-PCR and Western blot (WB). Additionally, the myocardial expression of TNF-α and PGC-1α was measured (RT-PCR) and Troponin I, myosin and phosphorylated Akt/Akt (pAkt/Akt) were quantified (WB).
Results: MuRF1 and MAFbx expression were significantly reduced in biopsies from MI patients. TNF-α 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 C, whereas the myosin expression was not altered. Compared to C, pAkt/Akt was elevated, whereas PGC-1α was downregulated.
Conclusion: The results of the present study suggest for the first time that the atrogenes MuRF1/MAFbx are involved in regulating the hypertrophic response, characteristic of the early post-infarction remodelling 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-α needs to be confirmed in further experiments.