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

1127 Citations (Scopus)

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

Fingerprint

Endothelial cells
MicroRNAs
Blood Vessels
Vascular Endothelial Growth Factor A
Endothelial Cells
Angiogenesis Inhibitors
Blood vessels
Cell proliferation
Intercellular Signaling Peptides and Proteins
Animals
Repair
Angiogenesis Inducing Agents
Defects
Cell Movement
Myocardial Infarction
Maintenance
Cell Proliferation
Wounds and Injuries
mouse MIRN126 microRNA

Keywords

  • DEVBIO
  • RNA

ASJC Scopus subject areas

  • Developmental Biology

Cite this

The Endothelial-Specific MicroRNA miR-126 Governs Vascular Integrity and Angiogenesis. / Wang, Shusheng; Aurora, Arin B; Johnson, Brett A.; Qi, Xiaoxia; McAnally, John; Hill, Joseph A; Richardson, James A; Bassel-Duby, Rhonda S; Olson, Eric N.

In: Developmental Cell, Vol. 15, No. 2, 12.08.2008, p. 261-271.

Research output: Contribution to journalArticle

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