An Endothelial-Specific MicroRNA Regulates Embryonic Angiogenesis

A recent publication described a mechanism employed by the developing embryo to regulate formation of blood vessels.

Investigators at the University of Texas Southwestern Medical Center (Dallas, TX, USA) examined the role of endothelial cells, and in particular the role of an endothelial cell-specific microRNA, in the process of angiogenesis.

To this end, the investigators genetically engineered a line of mice to lack the microRNA miR-126. 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