SMAD4 and hereditary hemorrhagic telangiectasia: This role in endothelial cell survival suggests that in the presence of anti-proliferative and/or pro-apoptotic stimuli, decreased activity of the endoglin/ALK1/Smad4 route, as occurs in HHT patients, may lead to reduced cell proliferation and/or apoptosis in capillaries, leading to the vascular lesion.