TY - JOUR
T1 - TWIST1 regulates the activity of ubiquitin proteasome system via the miR-199/214 cluster in human end-stage dilated cardiomyopathy
AU - Baumgarten, Anna
AU - Bang, Claudia
AU - Tschirner, Anika
AU - Engelmann, Anke
AU - Adams, Volker
AU - Von Haehling, Stephan
AU - Doehner, Wolfram
AU - Pregla, Reinhard
AU - Anker, Markus S.
AU - Blecharz, Kinga
AU - Meyer, Rudolf
AU - Hetzer, Roland
AU - Anker, Stefan D.
AU - Thum, Thomas
AU - Springer, Jochen
PY - 2013/9/30
Y1 - 2013/9/30
N2 - Background: The transcription factor TWIST1 has been described to regulate the microRNA (miR)-199/214 cluster. Genetic disruption of TWIST1 resulted in a cachectic phenotype and early death of the knock-out mice. This might be connected to the activity of the ubiquitin-proteasome-system (UPS), as miR-199a has been suggested to regulate the ubiquitin E2 ligases Ube2i and Ube2g1. Methods: Cardiac tissue from explanted hearts of 42 patients with dilated cardiomyopathy and 20 healthy donor hearts were analysed for protein expression of TWIST1 and its inhibitors Id-1, MuRF-1 and MAFbx, the expression of miR-199a, -199b and -214, as well as the activity of the UPS by using specific fluorogenic substrates. Results: TWIST1 was repressed in patients with dilated cardiomyopathy by 43% (p=0.003), while Id1 expression was unchanged. This was paralleled by a reduced expression of miR-199a by 38±9% (p=0.053), miR-199b by 36±13% (p=0.019) and miR-214 by 41±11% (p=0.0158) compared to donor hearts. An increased peptidylglutamyl-peptide-hydrolysing activity (p
AB - Background: The transcription factor TWIST1 has been described to regulate the microRNA (miR)-199/214 cluster. Genetic disruption of TWIST1 resulted in a cachectic phenotype and early death of the knock-out mice. This might be connected to the activity of the ubiquitin-proteasome-system (UPS), as miR-199a has been suggested to regulate the ubiquitin E2 ligases Ube2i and Ube2g1. Methods: Cardiac tissue from explanted hearts of 42 patients with dilated cardiomyopathy and 20 healthy donor hearts were analysed for protein expression of TWIST1 and its inhibitors Id-1, MuRF-1 and MAFbx, the expression of miR-199a, -199b and -214, as well as the activity of the UPS by using specific fluorogenic substrates. Results: TWIST1 was repressed in patients with dilated cardiomyopathy by 43% (p=0.003), while Id1 expression was unchanged. This was paralleled by a reduced expression of miR-199a by 38±9% (p=0.053), miR-199b by 36±13% (p=0.019) and miR-214 by 41±11% (p=0.0158) compared to donor hearts. An increased peptidylglutamyl-peptide-hydrolysing activity (p
KW - Cardiomyopathy
KW - DCM
KW - MicroRNA
KW - TWIST1
KW - Ubiquitin proteasome system
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U2 - 10.1016/j.ijcard.2012.12.094
DO - 10.1016/j.ijcard.2012.12.094
M3 - Article
C2 - 23360823
AN - SCOPUS:84885330287
VL - 168
SP - 1447
EP - 1452
JO - International Journal of Cardiology
JF - International Journal of Cardiology
SN - 0167-5273
IS - 2
ER -