title: NADPH oxidase 4 is expressed in pulmonary artery adventitia and contributes to hypertensive vascular remodeling.
abstract: OBJECTIVE
  Pulmonary hypertension (PH) is a progressive disease arising from remodeling and narrowing of pulmonary arteries (PAs) resulting in high pulmonary blood pressure and ultimately right ventricular failure. Elevated production of reactive oxygen species by NADPH oxidase 4 (Nox4) is associated with increased pressure in PH. However, the cellular location of Nox4 and its contribution to aberrant vascular remodeling in PH remains poorly understood. Therefore, we sought to identify the vascular cells expressing Nox4 in PAs and determine the functional relevance of Nox4 in PH.
  
  
  RESULTS
  Elevated expression of Nox4 was detected in hypertensive PAs from 3 rat PH models and human PH using qualititative real-time reverse transcription polymerase chain reaction, Western blot, and immunofluorescence. In the vascular wall, Nox4 was detected in both endothelium and adventitia, and perivascular staining was prominently increased in hypertensive lung sections, colocalizing with cells expressing fibroblast and monocyte markers and matching the adventitial location of reactive oxygen species production. Small-molecule inhibitors of Nox4 reduced adventitial reactive oxygen species generation and vascular remodeling as well as ameliorating right ventricular hypertrophy and noninvasive indices of PA stiffness in monocrotaline-treated rats as determined by morphometric analysis and high-resolution digital ultrasound. Nox4 inhibitors improved PH in both prevention and reversal protocols and reduced the expression of fibroblast markers in isolated PAs. In fibroblasts, Nox4 overexpression stimulated migration and proliferation and was necessary for matrix gene expression.
  
  
  CONCLUSIONS
  These findings indicate that Nox4 is prominently expressed in the adventitia and contributes to altered fibroblast behavior, hypertensive vascular remodeling, and development of PH.
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary. sbarman@gru.edu dfulton@gru.edu fchen@gru.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Barman
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary. sbarman@gru.edu dfulton@gru.edu fchen@gru.edu.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Su
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Christiana
authors.initials: C
authors.lastname: Dimitropoulou
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Yusi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: John D
authors.initials: JD
authors.lastname: Catravas
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Weihong
authors.initials: W
authors.lastname: Han
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Orfi
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szantai-Kis
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Keri
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Istvan
authors.initials: I
authors.lastname: Szabadkai
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Nektarios
authors.initials: N
authors.lastname: Barabutis
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Olga
authors.initials: O
authors.lastname: Rafikova
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Rafikov
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Black
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Danny
authors.initials: D
authors.lastname: Jonigk
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Athanassios
authors.initials: A
authors.lastname: Giannis
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Reto
authors.initials: R
authors.lastname: Asmis
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: David W
authors.initials: DW
authors.lastname: Stepp
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary.
authors.forename: Ganesan
authors.initials: G
authors.lastname: Ramesh
authors.affiliation: From the Department of Forensic Medicine, Nanjing Medical University, Jiangsu, China (F.C.); Department of Pharmacology and Toxicology (S.A.B., Y.S., W.H., D.J.R.F.) and Vascular Biology Center (F.C., C.D., Y.W., J.D.S., N.B., O.R., R.R., S.M.B., D.W.S., G.R., D.J.R.F.), Georgia Regents University, Augusta; Vichem Chemie, Ltd, Budapest, Hungary (L.O., C.S.-K., G.K., I.S.); Institute for Organic Chemistry, University of Leipzig, Leipzig, Germany (A.G.); Institute for Pathology, Hannover Medical School, Hannover, Germany (D.J.); Departments of Clinical Laboratories and Biochemistry, University of Texas Health Science Center at San Antonio (R.A.); and Pathobiochemical Research Group of Hungarian Academy of Sciences (G.K.) and Department of Pharmaceutical Chemistry (L.O.), Semmelweis University, Budapest, Hungary. sbarman@gru.edu dfulton@gru.edu fchen@gru.edu.
authors.forename: David J R
authors.initials: DJ
authors.lastname: Fulton
mesh_terms: D063194:Adventitia / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism; D065627:Familial Primary Pulmonary Hypertension; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology / Q000235:genetics / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D000860:Hypoxia / Q000150:complications; D007211:Indoles; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016686:Monocrotaline; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D011758:Pyrroles; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D011758:Pyrroles; D017382:Reactive Oxygen Species; C116890:Semaxinib; D016686:Monocrotaline; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; C422943:Nox4 protein, mouse; C498911:Nox4 protein, rat
keywords: NADPH oxidase; adventitia; fibroblast; pulmonary artery