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

Nat Med. 2014 Apr;20(4):368-76. doi: 10.1038/nm.3487. Epub 2014 Mar 2.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / genetics*
  • Calcium-Binding Proteins
  • Carotid Artery Injuries / metabolism
  • Cell Proliferation
  • Down-Regulation
  • Endothelial Cells
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Intercellular Signaling Peptides and Proteins / physiology
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics*
  • MicroRNAs / physiology


  • Apolipoproteins E
  • Calcium-Binding Proteins
  • Dlk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • MIRN126 microRNA, mouse
  • MicroRNAs

Associated data

  • GEO/GSE34262