title: The role of cyclooxygenase-2 in the protection against apoptosis in vascular endothelial cells induced by cigarette smoking.
abstract: BACKGROUND
  Apoptosis has been demonstrated to be an important upstream event in the pathogenesis of chronic obstructive pulmonary disease (COPD). Cyclooxygenase-2 (COX-2) seems to be biologically relevant in COPD. However, the role of COX-2 in the apoptosis in vascular endothelial cells induced by cigarette smoke extract (CSE) remains to be elucidated. Our recent study found that the prostacyclin, one of the COX products in the microvascular endothelium, inhibited apoptosis in the emphysematous lungs of rats induced by CSE. In order to clarify the role of COX-2 in the apoptosis of vascular endothelial cells induced by CSE, we performed the present experiment to elucidate it.
  
  
  METHODS
  Twenty surgical lung specimens were obtained from 6 patients with COPD, 7 smoking controls and seven nonsmoking controls. The apoptotic index (AI) and COX-2 protein expression were detected in lung tissues. To further investigate the effects of CSE on the apoptosis and COX-2 expression in a human vascular endothelial cell line, the apoptosis rate and COX-2 expression were examined in human umbilical vein endothelial cells (ECV304) under exposure to varied concentrations of CSE as well as under exposure to 5.0% CSE for varied durations. Repeatedly, the apoptosis rate and COX-2 expression in ECV304 cells under 5.0% CSE were examined after exposing to varied concentrations of celecoxib, a highly selective COX-2 inhibitor.
  
  
  RESULTS
  Significantly increased AI and expression of COX-2 were found both in the lungs of patients with COPD and smoking controls compared with nonsmoking controls. The CSE induced apoptosis in ECV304 cells in means of both dose-dependent and time-dependent manners. The COX-2 was slightly expressed in the cells after exposing to 5% CSE for 3 and 6 h, and markedly expressed after the exposure time for 9 and 12 h, but vanished after 24 h of the exposure. Of interest, with the completely block of the COX-2 expression by celecoxib at 50.0 µmol/L, the apoptosis rate was markedly increased again in ECV304 cells under exposure to 5.0% CSE.
  
  
  CONCLUSIONS
  Endothelial cell apoptosis and the expression of COX-2 protein were increased in both COPD patients and CSE-induced vascular endothelial cells. Of interest, it seems that the COX-2 probably had a protective role against the apoptosis in the vascular endothelial cells induced by cigarette smoking.
authors.affiliation: Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, Changsha 410011, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, Changsha 410011, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, Changsha 410011, China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, Changsha 410011, China.
authors.forename: Yingjiao
authors.initials: Y
authors.lastname: Long
authors.affiliation: Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, Changsha 410011, China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Liu
authors.affiliation: Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, Changsha 410011, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, Changsha 410011, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
keywords: Cyclooxygenase-2 (COX-2); apoptosis; celecoxib; cigarette smoking extract (CSE); vascular endothelial cell