Change of extracellular signal-regulated kinase expression in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease.

BACKGROUND

Cigarette smoking may contribute to pulmonary hypertension in chronic obstructive pulmonary disease (COPD) by resulting in pulmonary vascular remodeling that involves pulmonary artery smooth muscle cell (PASMC) proliferation. However, the molecular mechanism underlying this process remains poorly understood.

OBJECTIVES

The purpose of this study was to investigate the role of extracellular signal-regulated kinase (ERK) in pulmonary arteries from smokers with normal lung function and smokers with mild to moderate COPD.

METHODS

The peripheral lung tissues were obtained from 14 nonsmokers with normal lung function, 18 smokers with normal lung function, and 16 smokers with mild to moderate COPD. The morphological changes of pulmonary arteries were observed by hematoxylin-eosin (HE) staining. Primary cultured human pulmonary artery smooth muscle cells (HPASMCs) were exposed to cigarette smoke extract (CSE). Cell proliferation was determined by cell counting and Methyl thiazolyl tetrazolium assay. Protein expression was analyzed by western blotting.

RESULTS

Morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than that in nonsmoker group (P < .01). The protein level of ERK was significantly increased in smoker group and COPD group as compared with nonsmoker group (P < .01). The expression of ERK was significantly increased in HPASMCs at protein levels when HPASMCs were treated with 5% CSE (P < .01), which significantly promoted the proliferation of HPASMCs (P < .01).

CONCLUSIONS

Increased expression of ERK might be involved in the pathogenesis of abnormal proliferation of PASMCs in smokers with and without COPD.