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Expression of vascular endothelial growth factor (VEGF) in lung tissue of smokers and COPD

흡연자와 COPD환자에서 혈관내피 성장인자의 발현

초록/요약

Background: Although chronic obstructive pulmonary disease (COPD) is a major worldwide health problem, its exact mechanism of initiation and progression are not completely understood. Vascular endothelial growth factor (VEGF) signaling is crucial for lung structure maintenance and recent reports have indicated that it is involved in several lung disorders including COPD. This study was performed to evaluate the role of VEGF in the pathogenesis of COPD by examining the expressions of VEGF and its receptors in lung tissue. Methods: Twenty-nine subjects enrolled and divided into three groups; non-smokers with normal lung function (non-smokers, n=10), smokers without COPD (healthy smokers, n=9), and smokers with COPD (COPD, n=10). The expression of VEGF and its receptors were analyzed in each group by immunohistochemical staining at various parts of lung tissue using a semiquantitative scoring method and western blotting. The correlation between VEGF and lung function test parameters was examined. Finally, the expression of hypoxia inducible factor-1α (HIF-1α) in each group was evaluated. Results: Compared with healthy smokers, VEGF expression in COPD was significantly increased in the bronchiolar epithelium and vascular smooth muscle. Significantly increased expression of VEGF receptor (VEGFR)-2 was found in bronchiolar and vascular smooth muscle (p < 0.05). Forced expiratory volume in 1 second was negatively correlated with the VEGF expression in bronchiolar epithelium (r = -0.58), bronchiolar smooth muscle(r = -0.40), and vascular smooth muscle (r = -0.65, p < 0.05). The increased expressions of VEGF and VEGFR-2 were also shown in western blot. The level of HIF-1α was also increased in COPD and positively correlated with those of VEGF (r = 0.39, p < 0.01). Additional analysis for the patients with chronic bronchitis (CB) among COPD demonstrated that the increased expression of VEGF compared with healthy smokers and correlation between VEGF and HIF-1α expression were more prominent than those in the analysis for the patients with COPD. Conclusions: VEGF overexpression may be the characteristic of COPD, especially CB type. HIF-1α seems to be associated with increased expression of VEGF. HIF-1α -VEGF signaling may be involved in the pathogenesis of COPD.

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Korean Abstract ⅰ
Abstract ⅲ
Ⅰ. Introduction 1

Ⅱ. Materials and Methods 4

Ⅲ. Results 8

Ⅳ. Discussion 13

Ⅴ. Conclusions 18

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