Boron ion is essential in metabolism and its concentration is regulated by ion-channel NaBC1. NaBC1 mutations cause corneal dystrophies such as Harboyan syndrome. Here a 3D molecular model for NaBC1 is proposed and it is shown that simultaneous stimulation of NaBC1 and vascular endothelial growth factor receptors (VEGFR) promotes angiogenesis in vitro and in vivo with ultralow concentrations of VEGF. Human umbilical vein endothelial cells' (HUVEC) organization into tubular structures is shown to be indicative of vascularization potential. Enhanced cell sprouting is found only in the presence of VEGF and boron, the effect abrogated after blocking NaBC1. It is demonstrated that stimulated NaBC1 promotes angiogenesis via PI3k-independent pathways and that α5 β1 /αv β3 integrin binding is not essential to enhanced HUVEC organization. A novel vascularization mechanism that involves crosstalk and colocalization between NaBC1 and VEGFR receptors is described. This has important translational consequences; just by administering boron, taking advantage of endogenous VEGF, in vivo vascularization is shown in a chorioallantoic membrane assay.

Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 76 32300 Pilsen Czech Republic

Biomedical Research Networking Center in Bioengineering Biomaterials and Nanomedicine Universitat Politècnica de València Camino de Vera s n 46022 Valencia Spain

Center for Biomaterials and Tissue Engineering Universitat Politècnica de València Camino de Vera s n 46022 Valencia Spain

Centre for the Cellular Microenvironment School of Engineering University of Glasgow G12 8LT Glasgow UK

Departament de Bioquímica i Biologia Molecular Universitat de València Doctor Moliner s n 46100 Burjassot Spain

Instituto de Biología Molecular y Celular de Plantas Centro Superior de Investigaciones Científicas Universitat Politècnica de València Camino de Vera s n 46022 Valencia Spain

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