Primary human aortic endothelial cells (HAEC) were treated with siRNA targeting Notch or ALK pathways compared to non-targeting (NT) siRNA. A–C) Suppression of Notch1 (siN1), Notch2 (siN2), or Notch4 (siN4) was validated by immunoblot (8%, 14%, and 22% of NT, respectively). HAEC were treated with ligand as indicated, and proliferation measured by BrdU incorporation. D) HAEC targeted with siN1 or NT siRNA were treated with ligands, and HEY1 mRNA quantified by qPCR. E) HAEC were treated with vehicle or ligands for 24h and whole cell lysates were immunoblotted for cleaved, activated forms of Notch1 (V1744), Notch2 (D1733/A1734), or Notch4 (V1432), and quantified in comparison to β-actin (F). G) siRNA was used to suppress RBPJ (siRBPJ), and cell lysates were immunoblotted to confirm loss of protein (10% of NT). Proliferation was measured using BrdU incorporation. Similar knockdown experiments targeted ALK1 (H, siALK1, 17% of NT) or Smad1/5/9 (I, siSmad1/5, 19% of NT). Graphed are means ±SD. (*) signifies statistical significance with p<0.05. (†) signifies statistically significant reversal of effects (p<0.05).