Authors
Amin Damanafshan, Ies Elzenaar, Benoit Samson-Couterie, Ingeborg Van Der Made, Meriem Bourajjaj, Maarten M Van Den Hoogenhof, Henk A Van Veen, Daisy I Picavet, Abdelaziz Beqqali, Elisabeth Ehler, Leon J De Windt, Yigal M Pinto, Ralph J Van Oort
Publication date
2018/9/1
Journal
Cardiovascular research
Volume
114
Issue
11
Pages
1474-1486
Publisher
Oxford University Press
Description
Aims
The pathology of heart failure is characterized by poorly contracting and dilated ventricles. At the cellular level, this is associated with lengthening of individual cardiomyocytes and loss of sarcomeres. While it is known that the transcription factor myocyte enhancer factor-2 (MEF2) is involved in this cardiomyocyte remodelling, the underlying mechanism remains to be elucidated. Here, we aim to mechanistically link MEF2 target genes with loss of sarcomeres during cardiomyocyte remodelling.
Methods and results
Neonatal rat cardiomyocytes overexpressing MEF2 elongated and lost their sarcomeric structure. We identified myotonic dystrophy protein kinase (DMPK) as direct MEF2 target gene involved in this process. Adenoviral overexpression of DMPK E, the isoform upregulated in heart failure, resulted in severe loss of sarcomeres in vitro, and transgenic mice …
Scholar articles
A Damanafshan, I Elzenaar, B Samson-Couterie… - Cardiovascular research, 2018