An Endothelial-specific microRNA Governs Vascular Integrity and Angiogenesis

By Shusheng Wang, A. Aurora, Brett A. Johnson, X. Qi, John R. McAnally, Joseph A. Hill, J. Richardson, R. Bassel-Duby, E. Olson. Developmental Cell, 2008

1,829 citations recorded by the source corpus.

SUMMARY 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 pro-angiogenic 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.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9d04b20797f780ff2be1cf721d6b8eef8f7e18be

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Citations in the corpus

Delivery of MicroRNA-126 by Apoptotic Bodies Induces CXCL12-Dependent Vascular Protection (2009, methodology): “H. A. Golpon, V. A. Fadok, L. Taraseviciene-Stewart, R. Scerbavicius, C. Sauer, T. Welte, P. M. Henson, N. F. Voelkel, Life after corpse engulfment: Phagocytosis of apoptotic cells leads to VEGF secretion and cell growth.”
miR-375 maintains normal pancreatic α- and β-cell mass (2009, background): “For instance, tissue-enriched miRNAs in the heart, such as miR-1, miR-208, and miR-133, have been shown to regulate the hypertrophic proliferative activity in response to a variety of stresses, and miR-126 affects survival after induction of a myocardial infarction (7, 12, 33).”
Pathophysiology of Atherosclerosis (2022, background): “On the other hand, miR-126 acts as an intercellular messenger mainly released by ECs and internalized primarily by monocytes and VSMCs [311].”
MicroRNAs in stress signaling and human disease (2012, background): “miR-126 knockout mice have fragile, leaky vessels and display impaired angiogenesis in response to injury and angiogenic signaling (Kuhnert et al., 2008; Wang et al., 2008).”
Metazoan MicroRNAs (2018, background): “…hemorrhaging due to loss of vascular integrity and defects in endothelial cell proliferation, migration, and angiogenesis (Kuhnert et al., 2008; Wang et al., 2008); defects in innate immune response (Agudo et al., 2014); exacerbated atherosclerosis in sensitized background (Apoe) (Schober et…”
Biological functions of microRNAs: a review (2011, background): “Quite recently, Wang et al. [ 66 ] found that an endothelial cell-restricted miR-126 mediates developmental angiogenesis in vivo.”
MicroRNAs in development and disease. (2011, background): “(652) show for the first time through gain- and loss-of-function experiments in an aortic ring sprouting assay that Spred-1 is sufficient for inhibiting vascular outgrowths (652).”
New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis (2018, background): “Hyperglycemia also decreases anti-inflammatory protein A20 expression via O-glucosamine-N-acetylation-dependent ubiquitination and proteasomal degradation in response to inflammatory stimuli in VSMCs and endothelial cells [52].”