Role of growth factors and extracellular matrix regulators in airway remodeling in COPD

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disorder of the lungs, becoming a global health problem with increasing morbidity and mortality. Recent observations indicate that COPD is the fourth cause of mortality in the USA and it is projected to be the fifth burden of morbidity world-wide in the year 2020 according to a consensus report published by the World Health Organisation. COPD is characterized by a slow progression of airflow limitation, which is nearly irreversible. Recently, the Global Initiative on Obstructive Lung Disease (GOLD) has formulated an official definition; “A disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lungs to noxious particles and gases”. One of the major determining factors is tobacco smoking, but it remains to be investigated to what extent other factors such as environmental and occupational exposures and genetic factors can contribute to the disease. Surprisingly, only 10-20 percent of all smokers develop COPD

Enhanced expression of fibroblast growth factors and receptor FGFR-1 during vascular remodeling in chronic obstructive pulmonary disease

Important characteristics of chronic obstructive pulmonary disease (COPD) include airway and vascular remodeling, the molecular mechanisms of which are poorly understood. We assessed the role of fibroblast growth factors (FGF) in pulmonary vascular remodeling by examining the expression pattern of FGF-1, FGF-2, and the FGF receptor (FGFR-1) in peripheral area of lung tissues from patients with COPD (FEV(1) < or = 75%; n = 15) and without COPD (FEV(1) > or = 85%; n = 13). Immunohistochemical staining results were evaluated by digital video image analysis as well as by manual scoring. FGF-1 and FGFR-1 were detected in vascular smooth muscle (VSM), airway smooth muscle, and airway epithelial cells. FGF-2 was localized in the cytoplasm of airway epithelium and in the nuclei of airway smooth muscle, VSM, and endothelial cells. In COPD cases, an unequivocal increase in FGF-2 expression was observed in VSM (3-fold, P = 0.001) and endothelium (2-fold, P = 0.007) of small pulmonary vessels with a luminal diameter under 200 micro m. In addition, FGFR-1 levels were elevated in the intima (1.5-fold, P = 0.05). VSM cells of large (> 200 micro m) pulmonary vessels showed increased staining for FGF-1 (1.6-fold, P < 0.03) and FGFR-1 (1.4-fold, P < 0.04) in COPD. Pulmonary vascular remodeling, assessed as the ratio of alpha-smooth muscle actin staining and vascular wall area with the lumen diameter, was increased in large vessels of patients with COPD (P = 0.007) and was inversely correlated with FEV(1) values (P < 0.007). Our results suggest an autocrine role of the FGF-FGFR-1 system in the pathogenesis of COPD-associated vascular remodeling