Similarly, as activation of PI3-Kinase is downstream of both VEGF and ANGPT2, PI3-Kinase inhibitors have been tested and have proven efficacy in preclinical HHT models such as Alk1+/− mice or mice treated with neutralizing anti-BMP9/BMP10 antibodies [40, 42]. This evidence concerns the gene GDF2 and hereditary hemorrhagic telangiectasia.