Schematic Illustration of How Thalidomide Normalizes Vascular Malformations in HHT. a) Reduced expression of endoglin or ALK-1 in endothelial cells reduces pericyte recruitment. Smooth muscle cell coverage of arteries is irregular, and vessels show endothelial hyperplasia and irregular capillary diameter. b) A low dose of thalidomide normalizes vessel coverage defects and excessive angiogenesis by stimulating mural cell recruitment. Mechanisms of thalidomide-induced vessel maturation include increased PDGF-B expression from the endothelial tip cells, which attracts co-migrating mural cells, and direct stimulation of mural cell proliferation. c) A high dose of thalidomide enhances the number of mural cells expressing α-SMA, indicating vessel maturity, and inhibits angiogenesis. Black arrows indicate that thalidomide targets both endothelial tip cells and mural cells directly to control vessel growth and maturation. a = artery; v = vein. Schematic illustration of how thalidomide normalizes vascular malformations in HHT.Figure Reprinted with permission from Macmillan Publishers Ltd: Nature Medicine (Lebrin F, Srun S, Raymond R, et al. Nat Med. 2010;16:420-428.) Copyright 2010.