title: Endothelial cell dysfunction and cross talk between endothelium and smooth muscle cells in pulmonary arterial hypertension.
abstract: The pathogenesis of pulmonary arterial hypertension (PAH) involves a complex and multifactorial process in which endothelial cell dysfunction appears to play an integral role in mediating the structural changes in the pulmonary vasculature. Disordered endothelial cell proliferation along with concurrent neoangiogenesis, when exuberant, results in the formation of glomeruloid structures known as the plexiform lesions, which are common pathological features of the pulmonary vessels of patients with PAH. In addition, an altered production of various endothelial vasoactive mediators, such as nitric oxide, prostacyclin, endothelin-1, serotonin, chemokines and thromboxane, has been increasingly recognized in patients with PAH. Because most of these mediators affect the growth of the smooth muscle cells, an alteration in their production may facilitate the development of pulmonary vascular hypertrophy and structural remodeling characteristic of PAH. It is conceivable that the beneficial effects of many of the treatments currently available for PAH, such as the use of prostacyclin, nitric oxide, and endothelin receptor antagonists, result at least in part from restoring the balance between these mediators. A greater understanding of the role of the endothelium in PAH will presumably facilitate the evolution of newer, targeted therapies.
authors.affiliation: Université Paris-Sud 11, Centre National de Référence de l'Hypertension Artérielle Pulmonaire, Service de Pneumologie et Réanimation Respiratoire, Hôpital Antoine-Béclère, Assistance Publique des Hôpitaux de Paris, Clamart, France. marc.humbert@abc.aphp.fr
authors.forename: Marc
authors.initials: M
authors.lastname: Humbert
authors.forename: David
authors.initials: D
authors.lastname: Montani
authors.forename: Frédéric
authors.initials: F
authors.lastname: Perros
authors.forename: Peter
authors.initials: P
authors.lastname: Dorfmüller
authors.forename: Serge
authors.initials: S
authors.lastname: Adnot
authors.forename: Saadia
authors.initials: S
authors.lastname: Eddahibi
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology; D018925:Chemokines / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D012701:Serotonin / Q000378:metabolism
chemical_list: D018925:Chemokines; D012701:Serotonin