Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury

Translated title of the contribution: Inhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury

J.M. Daniel, D. Penzkofer, R. Teske, J. Dutzmann, A. Koch, W. Bielenberg, A. Bonauer, R.A. Boon, A Fischer, J. Bauersachs, E. van Rooij, S. Dimmeler, D.G. Sedding

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 alpha 5 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 a5 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
Translated title of the contributionInhibition of miR-92a improves re-endothelialization and prevents neointima formation following vascular injury
Original languageUndefined/Unknown
Pages (from-to)564-572
Number of pages9
JournalCardiovascular Research
Volume103
Issue number4
Publication statusPublished - 2014

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