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http://purl.uniprot.org/citations/21788589http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21788589http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21788589http://www.w3.org/2000/01/rdf-schema#comment"

Background

Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood.

Methods and results

Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2-associated death promoter) and Sirtuin1 were identified by transcriptome, protein arrays, and chromatin immunoprecipitation analyses. Overexpression of miR-24 or silencing of its targets significantly impaired angiogenesis in zebrafish embryos. Blocking of endothelial miR-24 limited myocardial infarct size of mice via prevention of endothelial apoptosis and enhancement of vascularity, which led to preserved cardiac function and survival.

Conclusions

Our findings indicate that miR-24 acts as a critical regulator of endothelial cell apoptosis and angiogenesis and is suitable for therapeutic intervention in the setting of ischemic heart disease."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.org/dc/terms/identifier"doi:10.1161/circulationaha.111.039008"xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Gupta S.K."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Gupta S.K."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Tuschl T."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Tuschl T."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Fiedler J."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Fiedler J."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Engelhardt S."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Engelhardt S."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Hartmann D."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Hartmann D."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Lorenzen J."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Lorenzen J."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Martin U."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Martin U."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Heineke J."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Heineke J."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Brand T."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Brand T."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Schulte-Merker S."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Schulte-Merker S."xsd:string
http://purl.uniprot.org/citations/21788589http://purl.uniprot.org/core/author"Kneitz S."xsd:string
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