The Endothelial-Specific MicroRNA miR-126 Governs Vascular Integrity and Angiogenesis

Shusheng Wang, Arin B Aurora, Brett A. Johnson, Xiaoxia Qi, John McAnally, Joseph A Hill, James A Richardson, Rhonda S Bassel-Duby, Eric N Olson

Research output: Contribution to journalArticle

1232 Scopus citations

Abstract

Endothelial cells play essential roles in maintenance of vascular integrity, angiogenesis, and wound repair. We show that an endothelial cell-restricted microRNA (miR-126) mediates developmental angiogenesis in vivo. Targeted deletion of miR-126 in mice causes leaky vessels, hemorrhaging, and partial embryonic lethality, due to a loss of vascular integrity and defects in endothelial cell proliferation, migration, and angiogenesis. The subset of mutant animals that survives displays defective cardiac neovascularization following myocardial infarction. The vascular abnormalities of miR-126 mutant mice resemble the consequences of diminished signaling by angiogenic growth factors, such as VEGF and FGF. Accordingly, miR-126 enhances the proangiogenic actions of VEGF and FGF and promotes blood vessel formation by repressing the expression of Spred-1, an intracellular inhibitor of angiogenic signaling. These findings have important therapeutic implications for a variety of disorders involving abnormal angiogenesis and vascular leakage.

Original languageEnglish (US)
Pages (from-to)261-271
Number of pages11
JournalDevelopmental cell
Volume15
Issue number2
DOIs
StatePublished - Aug 12 2008

Keywords

  • DEVBIO
  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The Endothelial-Specific MicroRNA miR-126 Governs Vascular Integrity and Angiogenesis'. Together they form a unique fingerprint.

  • Cite this