title: Elevated expression of placental growth factor is associated with airway-wall vascular remodelling and thickening in smokers with asthma.
abstract: The increased expression of placental growth factor (PlGF) in chronic obstructive pulmonary disease and allergy-related asthma suggests its role in the pathogenesis of these diseases. In asthmatic smokers, airway remodelling is accompanied by an accelerated decline in lung function. However, whether PlGF contributes to the persistent airflow obstruction and vascular remodelling typically seen in asthmatic smokers is unknown. In this study we measured lung function, airway-wall thickening, and PlGF levels in serum and induced sputum in 74 asthmatic and 42 healthy smokers and never-smokers. Using human lung microvascular endothelial cells (HLMECs), we evaluated the in vitro effects of PlGF on each step of vascular remodelling, including proliferation, migration, stress-fibre expression, and tubule formation. Our data showed significantly higher serum and sputum PlGF levels in asthma patients, especially asthmatic smokers, than in healthy controls. Serum and sputum PlGF levels correlated negatively with post-bronchodilator forced expiratory volume in 1 s (FEV1) and the FEV1/forced vital capacity, but positively with airway-wall thickening. Stimulation of HLMECs with rhPlGF promoted all of the steps of airway-microvascular remodelling. These findings provide insights into the influence of cigarette smoking on the structural changes in the airways of asthmatics and the important pathogenic role played by PlGF.
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Tianwen
authors.initials: T
authors.lastname: Lai
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Yalian
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Radiology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Radiology, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Guihai
authors.initials: G
authors.lastname: Pan
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Binfan
authors.initials: B
authors.lastname: Yuan
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Quanchao
authors.initials: Q
authors.lastname: Lv
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Yanyu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Dongmin
authors.initials: D
authors.lastname: Li
authors.affiliation: Institute of Respiratory Diseases, Department of Respiratory, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
mesh_terms: D000328:Adult; D056151:Airway Remodeling / Q000502:physiology*; D001249:Asthma / Q000378:metabolism / Q000473:pathology*; D001980:Bronchi / Q000473:pathology; D016022:Case-Control Studies; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000502:physiology; D008297:Male; D000072483:Placenta Growth Factor / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D000074285:Smokers; D013183:Sputum / Q000378:metabolism; D066253:Vascular Remodeling / Q000502:physiology*; D014797:Vital Capacity
chemical_list: C000608036:PGF protein, human; D011994:Recombinant Proteins; D000072483:Placenta Growth Factor