MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1

By A. Schober, M. Nazari-Jahantigh, Yuanyuan Wei, K. Bidzhekov, F. Gremse, J. Grommes, R. Megens, K. Heyll, H. Noels, Michael Hristov and 4 more. Nature Medicine, 2014

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Atherosclerosis, a hyperlipidemia-induced chronic inflammatory process of the arterial wall, develops preferentially at sites where disturbed laminar flow compromises endothelial cell (EC) function. Here we show that endothelial miR-126-5p maintains a proliferative reserve in ECs through suppression of the Notch1 inhibitor delta-like 1 homolog (Dlk1) and thereby prevents atherosclerotic lesion formation. Endothelial recovery after denudation was impaired in Mir126−/− mice because lack of miR-126-5p, but not miR-126-3p, reduced EC proliferation by derepressing Dlk1. At nonpredilection sites, high miR-126-5p levels in endothelial cells confer a proliferative reserve that compensates for the antiproliferative effects of hyperlipidemia, such that atherosclerosis was exacerbated in Mir126−/− mice. In contrast, downregulation of miR-126-5p by disturbed flow abrogated EC proliferation at predilection sites in response to hyperlipidemic stress through upregulation of Dlk1 expression. Administration of miR-126-5p rescued EC proliferation at predilection sites and limited atherosclerosis, introducing a potential therapeutic approach.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ad2978f7fd90af431f321929ad11dfff1b83abf4

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Citations in the corpus

Metazoan MicroRNAs (2018, background): “, 2014); exacerbated atherosclerosis in sensitized background (Apoe) (Schober et al., 2014)”
Organotypic vasculature: From descriptive heterogeneity to functional pathophysiology (2017, background): “Endothelial miR126 limits atherosclerosis by targeting the noncanonical Notch ligand DLL1 (96).”