Fig. 5

Summary scheme. Under atheroprone LSS conditions (left), circulating BMP9 gets sequestrated by Endoglin, expressed on endothelial cells. Endoglin binds to the type II receptor interface, thereby blocking BMP type I/II receptor complex formation. Nonetheless, residual BMP9-ALK1-type II receptor signaling occurs at the plasma membrane. Upon internalization via caveolae, Endoglin gets substituted by type II receptors in EEs and exacerbated pSMAD1/5 signaling is induced which leads to the expression of mesenchymal and atheroprone genes. Under atheroprotective HSS conditions (right), BMP9 is bound by ALK1 and type II receptors as well as by Endoglin, the latter suppressing BMP9-type I/II receptor formation. Caveolin-mediated endocytosis is markedly reduced when compared to LSS and residual pSMAD1/5 signaling is originating from the plasma membrane rather than from CAV1⁺ EEs. Ultimately, HSS leads to the expression of genes responsible for EC identity and quiescence