Back to Search
Start Over
Endothelial MRTF-A mediates angiotensin II induced cardiac hypertrophy.
- Source :
-
Journal of Molecular & Cellular Cardiology . Mar2015, Vol. 80, p23-33. 11p. - Publication Year :
- 2015
-
Abstract
- Angiotensin II (Ang II) stimulates endothelin (ET-1) transcription, which contributes to cardiac hypertrophy and fibrosis. We have previously reported that myocardin related transcription factor A (MRTF-A) is indispensable for ET-1 transcription in vascular endothelial cells under hypoxic conditions, indicating that MRTF-A might mediate Ang II-induced pathological hypertrophy. Here we report that Ang II augmented the expression of MRTF-A in cultured endothelial cells and in the lungs of mice with cardiac hypertrophy. Over-expression of MRTF-A enhanced, whereas depletion of MRTF-A attenuated, transcriptional activation of ET-1 gene by Ang II. MRTF-A deficiency ameliorated Ang II induced cardiac hypertrophy and fibrosis in mice paralleling diminished synthesis and release of ET-1. Mechanistically, MRTF-A was recruited to the ET-1 promoter by c-Jun/c-Fos (AP-1) in response to Ang II treatment. Once bound, MRTF-A altered the chromatin structure by modulating histone acetylation and H3K4 methylation on the ET-1 promoter. More importantly, mice with endothelial-specific MRTF-A silencing by lentiviral particles phenocopied mice with systemic MRTF-A deletion in terms of Ang II-induced pathological hypertrophy. In conclusion, we data have unveiled a MRTF-A-containing complex that links ET-1 transactivation in endothelial cells to cardiac hypertrophy and fibrosis by Ang II. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00222828
- Volume :
- 80
- Database :
- Academic Search Index
- Journal :
- Journal of Molecular & Cellular Cardiology
- Publication Type :
- Academic Journal
- Accession number :
- 101253635
- Full Text :
- https://doi.org/10.1016/j.yjmcc.2014.11.009