PTEN (Phosphatase and Tensin Homolog) Connection in Hereditary Hemorrhagic Telangiectasia 2
- activin-receptor like kinase 1
- arteriovenous malformation
- hereditary hemorrhagic telangiectasia 2
- phosphatidylinositol 3-kinase
The hierarchical network of arteries, veins, and capillaries of our cardiovascular system is laid out during development, and further expanded and matured postnatally. Precise regulation of endothelial proliferation and behavior is needed during development and throughout life to maintain the proper architecture of the vasculature. In this issue, Alsina-Sanchis et al1 report that PTEN (phosphatase and tensin homolog) connects BMP-9 (bone morphogenic protein 9) activation of ALK-1 (activin-receptor-like kinase 1) to PI3K (phosphatidylinositol 3-kinase) signaling in endothelial cells and implicate PI3K-stimulated endothelial proliferation in arteriovenous malformation (AVM) in hereditary hemorrhagic telangiectasia 2 (HHT-2).
See accompanying article on page 1216
HHT is a rare autosomal dominant disorder that affects ≈1/5000 people. HHT-1 is caused by loss of function of one allele of a TGF-β (transforming growth factor-β) coreceptor called endoglin, whereas HHT-2 is caused by loss of function of ALK-1, a TGF-β family type I receptor known phosphorylate SMADs (suppressor of mothers against decapentaplegic) 1/5/8. In both HHT-1 and HHT-2, vascular overgrowth and malformations called telangiectasias occur focally throughout the body. The telangiectasias appear to arise from abnormal connections between enlarged postcapillary venules and arterioles, which results in fragile vessels prone to bleeding.2
Previous studies had revealed ALK-1 suppresses endothelial proliferation and that lack of Alk-1 in mice leads to vascular overgrowth and malformation,3,4 but precisely how ALK-1 controls vascular growth and morphogenesis was unknown.