Hypoxia-inducible factor-1alpha and -2alpha additively promote endothelial vasculogenic properties.


OBJECTIVE While both play a role in the transcriptional response of hypoxic endothelial cells (ECs), hypoxia-inducible factor-1alpha (HIF-1alpha) and HIF-2alpha differ in their transactivation sites, pointing at potentially different target genes. We studied the discrete and common effects of HIF-1alpha and HIF-2alpha on the cytokine expression and vasculogenic properties of ECs. METHODS AND RESULTS H5V and bovine aortic ECs were transfected to express HIF-1alpha, HIF-2alpha or both. Overexpression of HIF-1alpha or HIF-2alpha and, to a greater extent, cotransfection of HIF-1alpha and HIF-2alpha resulted in EC activation, as revealed by analysis of the adhesion capacities and adhesion molecule surface expression of ECs. From the paracrine aspect, conditioned medium from HIF-expressing ECs was found to promote the migration and tube formation capacity of wild-type ECs, mostly following HIF-1alpha and HIF-2alpha coexpression. Antibody arrays revealed altered expression of multiple cytokines, pointing at consistent additive effects of HIF-1alpha and HIF-2alpha on angiogenic protein expression. Finally, HIF-1alpha and HIF-2alpha additively promoted vessel formation in vivo, as demonstrated by a Matrigel angiogenesis assay. CONCLUSION Our results further clarify the functional roles of HIF-1alpha and HIF-2alpha in ECs and for the first time demonstrate a common contribution of HIF-1alpha and HIF-2alpha to vasculogenesis.

DOI: 10.1159/000181546

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@article{BenShoshan2009HypoxiainducibleFA, title={Hypoxia-inducible factor-1alpha and -2alpha additively promote endothelial vasculogenic properties.}, author={Jeremy Ben-Shoshan and Sofia Maysel-Auslender and Galia Luboshits and Iris Barshack and Sylvie Polak-Charcon and Eldad Tzahor and Gad Keren and Jacob George}, journal={Journal of vascular research}, year={2009}, volume={46 4}, pages={299-310} }