title: Gene expression profile of angiogenic factors in pulmonary arteries in COPD: relationship with vascular remodeling.
abstract: Pulmonary vessel remodeling in chronic obstructive pulmonary disease (COPD) involves changes in smooth muscle cell proliferation, which are highly dependent on the coordinated interaction of angiogenic-related growth factors. The purpose of the study was to investigate, in isolated pulmonary arteries (PA) from patients with COPD, the gene expression of 46 genes known to be modulators of the angiogenic process and/or involved in smooth muscle cell proliferation and to relate it to vascular remodeling. PA segments were isolated from 29 patients and classified into tertiles, according to intimal thickness. After RNA extraction, the gene expression was assessed by RT-PCR using TaqMan low-density arrays. The univariate analysis only showed upregulation of angiopoietin-2 (ANGPT-2) in remodeled PA (P < 0.05). The immunohistochemical expression of ANGPT-2 correlated with intimal enlargement (r = 0.42, P < 0.05). However, a combination of 10 factors in a multivariate discriminant analysis model explained up to 96% of the classification of the arteries. A network analysis of 46 genes showed major decentralization. In this network, the metalloproteinase-2 (MMP-2) was shown to be the bridge between intimal enlargement and fibrogenic factors. In COPD patients, plasma levels of ANGPT-2 were higher in current smokers or those with pulmonary hypertension. We conclude that an imbalance in ANGPT-2, combined with related factors such as VEGF, β-catenin, and MMP-2, may partially explain the structural derangements of the arterial wall. MMP-2 may act as a bridge channeling actions from the main fibrogenic factors.
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and.
authors.forename: Jéssica
authors.initials: J
authors.lastname: García-Lucio
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and.
authors.forename: Gemma
authors.initials: G
authors.lastname: Argemi
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
authors.forename: Olga
authors.initials: O
authors.lastname: Tura-Ceide
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and.
authors.forename: Marta
authors.initials: M
authors.lastname: Diez
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and.
authors.forename: Tanja
authors.initials: T
authors.lastname: Paul
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bonjoch
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and.
authors.forename: Nuria
authors.initials: N
authors.lastname: Coll-Bonfill
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Blanco
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Barberà
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and.
authors.forename: Melina M
authors.initials: MM
authors.lastname: Musri
authors.affiliation: Department of Pulmonary Medicine, Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; and Biomedical Research Networking Center on Respiratory Diseases (CIBERES), Madrid, Spain vpeinado@clinic.ub.es.
authors.forename: Victor I
authors.initials: VI
authors.lastname: Peinado
mesh_terms: D000368:Aged; D042702:Angiopoietin-2 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D011651:Pulmonary Artery / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D059467:Transcriptome; D017539:Tunica Intima / Q000378:metabolism; D066253:Vascular Remodeling
chemical_list: C586513:ANGPT2 protein, human; D042702:Angiopoietin-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2
keywords: COPD; angiopoietin; gene expression profile; pulmonary artery; vascular remodeling