title: Connexin-mediated regulation of the pulmonary vasculature.
abstract: Pulmonary arterial hypertension (PAH) is a complex, multi-factorial disorder characterized by both constriction and remodelling of the distal pulmonary vasculature. This leads to increased pulmonary pressures and eventually right heart failure. Current drugs, which primarily target the vasoconstriction, serve only to prolong life and novel therapies targeting both the vasoconstriction and the remodelling are required. Aberrant signalling between cells of the pulmonary vasculature has been associated with the development of PAH. In particular, endothelial dysfunction can lead to hyperplasia of the underlying medial layer. Connexins are a family of transmembrane proteins which can form intercellular communication channels known as gap junctions. This review will discuss recent evidence which shows that connexins play a role in regulation of the pulmonary vasculature and that dysregulation of connexins may contribute to PAH pathogenesis. Interaction of connexins with signalling pathways relevant to the pathogenesis of PAH, such as bone morphogenetic protein (BMP), serotonin and oestrogen are discussed.
authors.affiliation: *School of Health and Life Sciences, Institute of Applied Health Research, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, U.K.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dempsie
authors.affiliation: *School of Health and Life Sciences, Institute of Applied Health Research, Glasgow Caledonian University, Cowcaddens Road, Glasgow G4 0BA, U.K.
authors.forename: Patricia
authors.initials: P
authors.lastname: Martin
authors.affiliation: †Department of Medicine; University of Cambridge School of Clinical Medicine, Addenborooke's Hospital, Cambridge CB2 0QQ, U.K.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Upton
mesh_terms: D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D017629:Gap Junctions / Q000235:genetics; D006333:Heart Failure / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D011651:Pulmonary Artery / Q000378:metabolism* / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014661:Vasoconstriction / Q000235:genetics
chemical_list: D019485:Bone Morphogenetic Proteins; D017630:Connexins; D004967:Estrogens; D012701:Serotonin