Arteriovenous malformations in mice lacking activin receptor-like kinase-1

摘要: The mature circulatory system is comprised of two parallel, yet distinct, vascular networks that carry blood to and from the heart. Studies have suggested endothelial tubes are specified as arteries veins at earliest stages angiogenesis, before onset circulation. To understand molecular basis for arterial-venous identity, we focused our studies on a human dysplasia, hereditary haemorrhagic telangiectasia (HHT), wherein arterial venous beds fail remain distinct. Genetic demonstrated HHT can be caused by loss-of-function mutations in gene encoding activin receptor-like kinase-1 (ACVRL1; ref. 5). ACVRL1 encodes type I receptor TGF-beta superfamily growth factors. At stage development, mice lacking Acvrl1 develop large shunts between veins, downregulate Efnb2 confine intravascular haematopoiesis arteries. These die mid-gestation with severe arteriovenous malformations resulting fusion major veins. early loss anatomical, functional distinctions indicates required developing distinct beds.