title: Iron chelation inhibits the development of pulmonary vascular remodeling.
abstract: Reactive oxygen species (ROS) have been implicated in the pathogenesis of pulmonary hypertension. Because iron is an important regulator of ROS biology, this study examined the effects of iron chelation on the development of pulmonary vascular remodeling. The administration of an iron chelator, deferoxamine, to rats prevented chronic hypoxia-induced pulmonary hypertension and pulmonary vascular remodeling. Various iron chelators inhibited the growth of cultured pulmonary artery smooth muscle cells. Protein carbonylation, an important iron-dependent biological event, was promoted in association with pulmonary vascular remodeling and cell growth. A proteomic approach identified that Rho GDP-dissociation inhibitor (a negative regulator of RhoA) is carbonylated. In human plasma, the protein carbonyl content was significantly higher in patients with idiopathic pulmonary arterial hypertension than in healthy controls. These results suggest that iron plays an important role in the ROS-dependent mechanism underlying the development of pulmonary hypertension.
authors.affiliation: Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Wong
authors.forename: Ioana R
authors.initials: IR
authors.lastname: Preston
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Hill
authors.forename: Yuichiro J
authors.initials: YJ
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006830:Hydralazine / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000097:blood / Q000503:physiopathology / Q000517:prevention & control; D007502:Iron Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D050050:Protein Carbonylation; D011651:Pulmonary Artery / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D007502:Iron Chelating Agents; D017382:Reactive Oxygen Species; D014665:Vasodilator Agents; D062948:rho Guanine Nucleotide Dissociation Inhibitor alpha; D006830:Hydralazine; D003676:Deferoxamine