Figure 4

A hypothetical mechanism of pulmonary arterial hypertension. Sequence of events that leads from endothelial cell initial apoptosis to proliferation of apoptosis-resistant endothelial cells and vascular smooth muscle cells and endothlial-mesenchymal (SM-like) transdifferentiation. Apoptotic endothelial cells may release some kinds of factors that generate apoptosis-resistant proliferative endothelial cells, promote vascular smooth muscle cell proliferation and result in subsequent selection of progenitor-like cells leads to endothlial-mesenchymal (SM-like) transdifferentiation. These events may be a general mechanism for intimal and medial hypertrophy, muscularization of arterioles and complex vascular lesions. Definition of abbreviations: EC = endothelial cell; SMC = smooth muscle cell; SM-like = smooth muscle-like