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  Vascular importance of themiR-212/132 cluster.

Kumarswamy, R., Volkmann, I., Beermann, J., Napp, L. C., Jabs, O., Bhayadia, R., et al. (2014). Vascular importance of themiR-212/132 cluster. European Heart Journal, 35(45), 3224-3231. doi:10.1093/eurheartj/ehu344.

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Kumarswamy, R., Author
Volkmann, I., Author
Beermann, J., Author
Napp, L. C., Author
Jabs, O., Author
Bhayadia, R., Author
Melk, A., Author
Ucar, A.1, Author           
Chowdhury, K.2, Author           
Lorenzen, J. M., Author
Gupta, S. K., Author
Batkai, S., Author
Thum, T., Author
Affiliations:
1Research Group of Molecular Developmental Neurobiology, MPI for biophysical chemistry, Max Planck Society, ou_578587              
2Facility of Microarray Analyses, MPI for biophysical chemistry, Max Planck Society, ou_578589              

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Free keywords: Angiogenesis; MicroRNAs; Endothelial cells; Sirtuins; Vascular function
 Abstract: Rationale Many processes in endothelial cells including angiogenic responses are regulated by microRNAs. However, there is limited information available about their complex cross-talk in regulating certain endothelial functions. Aim The objective of this study is to identify endothelial functions of the pro-hypertrophic miR-212/132 cluster and its crosstalk with other microRNAs during development and disease. Methods and results We here show that anti-angiogenic stimulation by transforming growth factor-beta activates the microRNA-212/132 cluster by derepression of their transcriptional co-activator cAMP response element-binding protein (CREB)-binding protein (CBP) which is a novel target of a previously identified pro-angiogenic miRNA miR-30a-3p in endothelial cells. Surprisingly, despite having the same seed-sequence, miR-212 and miR-132 exerted differential effects on endothelial transcriptome regulation and cellular functions with stronger endothelial inhibitory effects caused by miR-212. These differences could be attributed to additional auxiliary binding of miR-212 to its targets. In vivo, deletion of the miR-212/132 cluster increased endothelial vasodilatory function, improved angiogenic responses during postnatal development and in adult mice. Conclusion Our results identify (i) a novel miRNA-cross-talk involving miR-30a-3p and miR-212, which led to suppression of important endothelial genes such as GAB1 and SIRT1 finally culminating in impaired endothelial function; and (ii) microRNAs may have different biological roles despite having the same seed sequence.

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Language(s): eng - English
 Dates: 2014-09-122014-12-01
 Publication Status: Issued
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 Rev. Type: Peer
 Identifiers: DOI: 10.1093/eurheartj/ehu344
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Title: European Heart Journal
Source Genre: Journal
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Pages: - Volume / Issue: 35 (45) Sequence Number: - Start / End Page: 3224 - 3231 Identifier: -