title: Perspectives on endothelial-to-mesenchymal transition: potential contribution to vascular remodeling in chronic pulmonary hypertension.
abstract: All forms of pulmonary hypertension are characterized by structural changes in pulmonary arteries. Increased numbers of cells expressing alpha-smooth muscle (alpha-SM) actin is a nearly universal finding in the remodeled artery. Traditionally, it was assumed that resident smooth muscle cells were the exclusive source of these newly appearing alpha-SM actin-expressing cells. However, rapidly emerging experimental evidence suggests other, alternative cellular sources of these cells. One possibility is that endothelial cells can transition into mesenchymal cells expressing alpha-SM actin and that this process contributes to the accumulation of SM-like cells in vascular pathologies. We review the evidence that endothelial-mesenchymal transition is an important contributor to cardiac and vascular development as well as to pathophysiological vascular remodeling. Recent work has provided evidence for the role of transforming growth factor-beta, Wnt, and Notch signaling in this process. The potential roles of matrix metalloproteinases and serine proteases are also discussed. Importantly, endothelial-mesenchymal transition may be reversible. Thus insights into the mechanisms controlling endothelial-mesenchymal transition are relevant to vascular remodeling and are important as we consider new therapies aimed at reversing pulmonary vascular remodeling.
authors: Laboratorio de Microscopia Electrónica, Servicio Autónomo Instituto de Biomedicina, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela.
authors: Enrique
authors: E
authors: Arciniegas
authors: Maria G
authors: MG
authors: Frid
authors: Ivor S
authors: IS
authors: Douglas
authors: Kurt R
authors: KR
authors: Stenmark
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology*; D002448:Cell Adhesion; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D008648:Mesoderm / Q000166:cytology*