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

• Published in: Developmental cell 2008-08, Vol.15 (2), p.261-271
• Main Authors: Wang, Shusheng, Aurora, Arin B., Johnson, Brett A., Qi, Xiaoxia, McAnally, John, Hill, Joseph A., Richardson, James A., Bassel-Duby, Rhonda, Olson, Eric N.
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Blood Vessels - abnormalities; Blood Vessels - ultrastructure; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; DEVBIO; Endothelial Cells - metabolism; Endothelium - blood supply; Endothelium - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Developmental; Gene Targeting; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Mice; Mice, Knockout; MicroRNAs - chemistry; MicroRNAs - genetics; MicroRNAs - metabolism; Models, Biological; Molecular and cellular biology; Molecular Sequence Data; Myocardial Infarction - pathology; Neovascularization, Physiologic; Organ Specificity; Proteins - genetics; Proteins - metabolism; Regulatory Sequences, Nucleic Acid - genetics; Repressor Proteins - metabolism; RNA; Signal Transduction; Survival Analysis; Transcription, Genetic
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2008.07.002

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.