Abstract 12832: MicroRNA-214 Inhibits Angiogenesis by Targeting Quaking and Reducing Angiogenic Growth Factor Release
Angiogenesis is essential for normal embryonic development and a critical component of many pathological conditions in adult tissues. MicroRNAs (miRNAs) have been shown to be indispensable for normal vascular development, but the exact regulation of angiogenesis by miRNAs has not been resolved. Previously, we have observed that miR-214 is differentially expressed in compensatory arteriogenesis. Here, we investigated the role of miR-214 in the process of angiogenesis by studying its function in both in vitro and in vivo models of angiogenesis.
Methods and Results MiRNA expression analysis showed that miR-214 is highly expressed in all major vascular cell types and in tissues with a vast vascular network. Ingenuity Systems pathway analysis demonstrated that miR-214’s predicted targets correlate with angiogenesis-associated biological functions. In vitro overexpression or inhibition of miR-214 in endothelial cells (ECs), respectively reduced or enhanced outgrowth of tubular sprouts in a spheroid-based angiogenesis assay. In vivo silencing of miR-214 by antagomirs enhanced the formation of a perfused vascular network in implanted matrigel plugs in mice, but did not significantly affect adaptive arteriogenesis in a mouse model of hind limb ischemia. Reporter gene analysis revealed that miR-214 directly targets Quaking (QKI), a protein critical for vascular development and remodeling. Antagomir-mediated silencing of miR-214 led to increased QKI levels in vivo and small interfering RNA-mediated knockdown of QKI in ECs decreased tubular sprouting in a similar fashion as miR-214 overexpression. Additionally, overexpression of miR-214 reduced the pro-angiogenic action of EC-conditioned medium, and the expression of VEGFA, whereas miR-214 silencing enhanced the angiogenic response and increased the secretion of several pro-angiogenic growth factors.
Conclusions Here, we report a novel role for miR-214 in regulating angiogenesis in vitro and in vivo, which presents miR-214 as a potential important target for pro- or anti-angiogenic therapies.
- © 2011 by American Heart Association, Inc.