Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury.
In: Cardiovascular Research, Jg. 103 (2014-09-01), Heft 4, S. 564-572
Online
academicJournal
Zugriff:
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. [ABSTRACT FROM AUTHOR]
Titel: |
Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury.
|
---|---|
Autor/in / Beteiligte Person: | 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. |
Link: | |
Zeitschrift: | Cardiovascular Research, Jg. 103 (2014-09-01), Heft 4, S. 564-572 |
Veröffentlichung: | 2014 |
Medientyp: | academicJournal |
ISSN: | 0008-6363 (print) |
DOI: | 10.1093/cvr/cvu162 |
Schlagwort: |
|
Sonstiges: |
|