TY - JOUR T1 - Endothelial-to-mesenchymal transition in pulmonary hypertension JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P2360 AU - Benoit Ranchoux AU - Catherine Rucker-Martin AU - Fabrice Antigny AU - Christine Péchoux AU - Aurélie Hautefort AU - Harm Jan Bogaard AU - Peter Dorfmüller AU - Florence Lecerf AU - Nicolas Raymond AU - Sophie Chat AU - Elie Fadel AU - Amal Houssaini AU - Serge Adnot AU - Gerald Simonneau AU - Marc Humbert AU - Sylvia Cohen-Kaminsky AU - Frederic Perros Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P2360.abstract N2 - BackgroundPulmonary hypertension (PH) involves a pulmonary vascular remodeling due to accumulation of α-smooth muscle actin (α-SMA)-expressing mesenchymal-like cells.AimTo demonstrate that endothelial-to-mesenchymal transition (EndoMT) is a source of α-SMA-expressing cells in PH lesions. This process allows endothelial cells (EC) to acquire a mesenchymal/myofibroblastic phenotype.MethodsWe studied EndoMT in explanted tissue from PH patient and from rat models (sugen-hypoxia [SuHx]- and monocrotaline [MCT]-induced PH). Endothelial and subendothelial cells phenotypes were analyzed by multiple staining in immunofluorescence and by electron and correlative microscopy. The loss of endothelial cell-cell junction which is essential for EndoMT was characterized by immunostaining and by Western Blot (WB) (VE-cadherin, p120). We measured the expression of master transcription factors for EndoMT like Twist-1 in both human tissue and PH models. Finally we used rapamycin in MCT-induced PH model to regulate EndoMT.ResultsEndothelial and mesenchymal markers were expressed in an opposite gradient direction in intimal and plexiform lesions of PAH lung, with a loss of cell-cell junctions between luminal EC. These findings were compatible with an active EndoMT process with transitional EC leaving the luminal layer to constitute the neointima and the core of the plexiform lesions. Moreover, ultrastructural observations and WB quantification supported ongoing EndoMT in PAH. EndoMT was also observed in both rat models and was successfully regulated by rapamycin in the MCT-induced PH.ConclusionsEndoMT participates in the vascular remodeling responsible for human and experimental PAH, and this may have therapeutic implications for PH. ER -