title: Heme oxygenase is expressed in human pulmonary artery smooth muscle where carbon monoxide has an anti-proliferative role.
abstract: Heme oxygenase is the rate-limiting enzyme in the catabolism of heme to carbon monoxide, bilirubin and free iron. Many cell types express heme oxygenase-2 constitutively while heme oxygenase-1 is induced at sites of inflammation and oxidative stress. In systemic blood vessels, carbon monoxide may have an important homeostatic role where, like its better-studied counterpart nitric oxide, it is emerging as a vasodilator and an inhibitor of proliferation. However, much less is known regarding the role of heme oxygenase and carbon monoxide in the pulmonary circulation where vascular responses are very different. Here, using primary cultures of human pulmonary artery smooth muscle cells, we present novel data showing that this cell type expresses heme oxygenase-2 constitutively and, in the presence of oxidants, can induce heme oxygenase-1. We also show that the carbon monoxide-releasing molecule, tricarbonyldichlororuthenium (II) dimer, potently and profoundly inhibits proliferation of human pulmonary artery smooth muscle cells. Pulmonary hypertension is a disease characterised by abnormal vascular smooth muscle cell growth and remodelling of the pulmonary vasculature. Our observations support the growing evidence that the heme oxygenase/carbon monoxide system may play a role in the pathology of pulmonary hypertension.
authors.affiliation: Unit of Critical Care, The Royal Brompton and Harefield N.H.S. Trust, Imperial College School of Medicine, Sydney Street, London SW3 6NP, UK.
authors.forename: Salome J
authors.initials: SJ
authors.lastname: Stanford
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Walters
authors.forename: Alison A
authors.initials: AA
authors.lastname: Hislop
authors.forename: Sheila G
authors.initials: SG
authors.lastname: Haworth
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Evans
authors.forename: Brian E
authors.initials: BE
authors.lastname: Mann
authors.forename: Roberto
authors.initials: R
authors.lastname: Motterlini
authors.forename: Jane A
authors.initials: JA
authors.lastname: Mitchell
mesh_terms: D015153:Blotting, Western; D002248:Carbon Monoxide / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D009131:Muscle, Smooth, Vascular / Q000201:enzymology* / Q000648:ultrastructure; D011651:Pulmonary Artery / Q000201:enzymology* / Q000648:ultrastructure
chemical_list: D008565:Membrane Proteins; D002248:Carbon Monoxide; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2