Endothelial Plasticity: Shifting Phenotypes through Force Feedback

Figure 1

Mechanisms of endothelial-mesenchymal transition. EndMT is induced by TGFβ-dependent and TGFβ-independent mechanisms. Canonically, TGFβ-induced activation of SMAD2/3 induces the expression of mesenchymal genes and repression of endothelial genes. Noncanonically, TGFβ-induced activation of Erk1/2 and p38 MAPK activate the transcription factor Snail which induces mesenchymal differentiation and inhibits VE-Cadherin expression. Inflammatory signals and increased ROS production facilitate EndMT by increasing endogenous TGFβ expression, in an NFκB-dependent manner, creating a feed forward signaling mechanism. AT1 receptor can induce EndMT through activation of NADPH oxidase, resulting in increased ROS production and reduction of eNOS expression and activity.