Thalgott JH, et al. - In Acvrl1^+/− mutant mice that exhibited hereditary hemorrhagic telangiectasia type 2 (HHT2) vascular lesions, researchers intended to study the mechanisms underlying ACVRL1 haploinsufficiency leading to pathological angiogenesis in HHT2. In vitro investigation for underlying disease mechanisms were also carried out by generating Acvrl1^+/− mouse embryonic stem cell lines that underwent sprouting angiogenesis. In addition, genetic complementation experiments were also performed. Whether the mechanisms seen in mice are conserved in humans was also investigated by assessing HHT2 plasma samples and skin biopsies. In this study, vascular endothelial growth factor receptor 1 (VEGFR1) was shown to play a key role in HHT2 pathogenesis. The mechanisms explaining abnormal response of HHT2 blood vessels to angiogenic signals were also mentioned. In Acvrl1^+/− endothelial cells, HHT2 vascular anomalies were seen to be induced by high VEGFR2 activity. Using anti-VEGF therapy in HHT2 was supported.