Abstract
Background: The recovery of endothelial cells (ECs) after vascular injury is mainly mediated by the proliferation of resident ECs, thereby reducing neointima formation. The RNase Dicer processes microRNAs (miRNAs) and regulates EC function by controlling miRNA-mediated regulation of gene expression. This study aimed to investigate the impact of miRNA biogenesis in ECs on endothelial repair during lesion formation after vascular injury. Methods and results: To study the effect of Dicer on ECs during neointima formation, conditional deletion of Dicer was induced in Apoe-/- mice (EC-Dicer(flox)) by tarnoxifen injection. Following wire-induced injury to carotid arteries of EC-Dicer(flox) mice, the EC recovery was impaired and the neointima formation and lesional macrophage accumulation was increased. Moreover, conditional deletion of Dicer in ECs diminished the expression of miR-126-5p in EC-Dicer(flox) mice. Notably, reconstitution of miR-126-5p in the injured arteries of EC-Dicer(flox) mice using miR-126-5p mimic, prevented the impaired endothelial recovery and increased lesion formation observed in EC-Dicer(flox) mice. Conclusions: Deficiency of endothelial Dicer diminished endothelial recovery and promoted neointima formation probably due to impaired miR-126-5p expression. Treatment with miR-126-5p mimics promotes endothelial recovery and thereby limits neointima formation. Thus, miR-126-5p therapy represents a potential approach to improve endothelial recovery and prevent restenosis following vascular injury.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| Fakultät: | Medizin |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| ISSN: | 0167-5273 |
| Sprache: | Englisch |
| Dokumenten ID: | 63164 |
| Datum der Veröffentlichung auf Open Access LMU: | 19. Jul. 2019, 12:12 |
| Letzte Änderungen: | 04. Nov. 2020, 13:41 |
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