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Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury
AIMS: MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ischaemia, but the effects of miR-92a on re-endothelialization and neointimal lesion formation after vascular injury remain elusive. We tested the effects of lowering miR-92a levels using specific...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145012/ https://www.ncbi.nlm.nih.gov/pubmed/25020912 http://dx.doi.org/10.1093/cvr/cvu162 |
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author | Daniel, Jan-Marcus Penzkofer, Daniela Teske, Rebecca Dutzmann, Jochen Koch, Alexander Bielenberg, Wiebke Bonauer, Angelika Boon, Reinier A. Fischer, Ariane Bauersachs, Johann van Rooij, Eva Dimmeler, Stefanie Sedding, Daniel G. |
author_facet | Daniel, Jan-Marcus Penzkofer, Daniela Teske, Rebecca Dutzmann, Jochen Koch, Alexander Bielenberg, Wiebke Bonauer, Angelika Boon, Reinier A. Fischer, Ariane Bauersachs, Johann van Rooij, Eva Dimmeler, Stefanie Sedding, Daniel G. |
author_sort | Daniel, Jan-Marcus |
collection | PubMed |
description | AIMS: MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ischaemia, but the effects of miR-92a on re-endothelialization and neointimal lesion formation after vascular injury remain elusive. We tested the effects of lowering miR-92a levels using specific locked nucleic acid (LNA)-based antimiRs as well as endothelial-specific knock out of miR-92a on re-endothelialization and neointimal formation after wire-induced injury of the femoral artery in mice. METHODS AND RESULTS: MiR-92a was significantly up-regulated in neointimal lesions following wire-induced injury. Pre-miR-92a overexpression resulted in repression of the direct miR-92a target genes integrin α5 and sirtuin1, and reduced eNOS expression in vitro. MiR-92a impaired proliferation and migration of endothelial cells but not smooth muscle cells. In vivo, systemic inhibition of miR-92a expression with LNA-modified antisense molecules resulted in a significant acceleration of re-endothelialization of the denuded vessel area. Genetic deletion of miR-92a in Tie2-expressing cells, representing mainly endothelial cells, enhanced re-endothelialization, whereas no phenotype was observed in mice lacking miR-92a expression in haematopoietic cells. The enhanced endothelial recovery was associated with reduced accumulation of leucocytes and inhibition of neointimal formation 21 days after injury and led to the de-repression of the miR-92a targets integrin α5 and sirtuin1. CONCLUSION: Our data indicate that inhibition of endothelial miR-92a attenuates neointimal lesion formation by accelerating re-endothelialization and thus represents a putative novel mechanism to enhance the functional recovery following vascular injury. |
format | Online Article Text |
id | pubmed-4145012 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-41450122014-08-27 Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury Daniel, Jan-Marcus Penzkofer, Daniela Teske, Rebecca Dutzmann, Jochen Koch, Alexander Bielenberg, Wiebke Bonauer, Angelika Boon, Reinier A. Fischer, Ariane Bauersachs, Johann van Rooij, Eva Dimmeler, Stefanie Sedding, Daniel G. Cardiovasc Res Original Articles AIMS: MicroRNA (miR)-92a is an important regulator of endothelial proliferation and angiogenesis after ischaemia, but the effects of miR-92a on re-endothelialization and neointimal lesion formation after vascular injury remain elusive. We tested the effects of lowering miR-92a levels using specific locked nucleic acid (LNA)-based antimiRs as well as endothelial-specific knock out of miR-92a on re-endothelialization and neointimal formation after wire-induced injury of the femoral artery in mice. METHODS AND RESULTS: MiR-92a was significantly up-regulated in neointimal lesions following wire-induced injury. Pre-miR-92a overexpression resulted in repression of the direct miR-92a target genes integrin α5 and sirtuin1, and reduced eNOS expression in vitro. MiR-92a impaired proliferation and migration of endothelial cells but not smooth muscle cells. In vivo, systemic inhibition of miR-92a expression with LNA-modified antisense molecules resulted in a significant acceleration of re-endothelialization of the denuded vessel area. Genetic deletion of miR-92a in Tie2-expressing cells, representing mainly endothelial cells, enhanced re-endothelialization, whereas no phenotype was observed in mice lacking miR-92a expression in haematopoietic cells. The enhanced endothelial recovery was associated with reduced accumulation of leucocytes and inhibition of neointimal formation 21 days after injury and led to the de-repression of the miR-92a targets integrin α5 and sirtuin1. CONCLUSION: Our data indicate that inhibition of endothelial miR-92a attenuates neointimal lesion formation by accelerating re-endothelialization and thus represents a putative novel mechanism to enhance the functional recovery following vascular injury. Oxford University Press 2014-09-01 2014-06-27 /pmc/articles/PMC4145012/ /pubmed/25020912 http://dx.doi.org/10.1093/cvr/cvu162 Text en © The Author 2014. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Original Articles Daniel, Jan-Marcus Penzkofer, Daniela Teske, Rebecca Dutzmann, Jochen Koch, Alexander Bielenberg, Wiebke Bonauer, Angelika Boon, Reinier A. Fischer, Ariane Bauersachs, Johann van Rooij, Eva Dimmeler, Stefanie Sedding, Daniel G. Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury |
title | Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury |
title_full | Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury |
title_fullStr | Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury |
title_full_unstemmed | Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury |
title_short | Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury |
title_sort | inhibition of mir-92a improves re-endothelialization and prevents neointima formation following vascular injury |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4145012/ https://www.ncbi.nlm.nih.gov/pubmed/25020912 http://dx.doi.org/10.1093/cvr/cvu162 |
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