An Endothelial-Specific MicroRNA Regulates Embryonic Angiogenesis

They reported in the August 12, 2008, online edition of the journal Developmental Cell that targeted deletion of miR-126 in mice caused leaky vessels, hemorrhaging, and partial embryonic lethality, due to a loss of vascular integrity and defects in endothelial cell proliferation, migration, and angiogenesis. In this study, more than 40% of embryos lacking miR-126 failed to survive. Those that were born seemed normal but found less able to recover from simulated heart attack. Almost all mice lacking miR-126 died within three weeks of induced myocardial infarction, while more than 70% of control mice survived for at least three weeks.

At the molecular level miR-126 apparently enhanced the proangiogenic actions of vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) and promoted blood vessel formation by repressing the expression of Spred-1, an intracellular inhibitor of angiogenic signaling.

"MicroRNA research represents a new frontier in understanding and treating human disease. This is just a hint of what can come,” said senior author Dr. Eric Olson, professor of molecular biology at the University of Texas Southwestern Medical Center. "Manipulating this microRNA provides a completely new way of addressing cardiovascular disorders.”

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University of Texas Southwestern Medical Center