Beraprost sodium attenuates cigarette smoke extract-induced apoptosis in vascular endothelial cells.
Apoptosis is now widely recognized as an important part of chronic obstructive pulmonary disease (COPD) pathogenesis. Our previous study demonstrated that a prostacyclin (PGI(2)) analogue (beraprost sodium, BPS) prevented cigarette smoke extract (CSE) induced apoptosis of the pulmonary endothelium in rats. So we determined to clarify the apoptosis of vascular endothelial cells in COPD patient and the role of prostacyclin in the protection against apoptosis in vascular endothelial cells induced by CSE. Surgical specimens were obtained from 12 patients with COPD and 10 controls, and the level of apoptosis, prostacyclin synthase (PGI(2)S) expression and 6-keto-PGF1α (a stable metabolite of PGI(2)) were detected. The apoptotic index (AI), caspase-3 activity, expression of caspase-3 and 6-keto-PGF1α were examined in human umbilical vein endothelial cells (HUVECs) under exposure to varied concentrations of CSE for 24 h as well as under exposure to 2.5 % CSE for varied durations. Then, HUVECs under 2.5 % CSE were exposed to varied concentrations of BPS for 24 h and observed the alteration and the level of cAMP. Increased AI, decreased expression of PGI(2)S and 6-keto-PGF1α, were found in the lungs of patients with COPD compared with controls. Moreover, CSE induced apoptosis in means of both dose-dependent and time-dependent manners, and reduced the level of 6-keto-PGF1α in HUVECs. And with the treatment of BPS, an enhanced level of cAMP and decreased apoptosis were detected. The deficiency of PGI(2) critically contributes to the COPD-associated endothelial dysfunction and apoptosis. And BPS protects against the apoptosis in the vascular endothelial cells induced by CSE.
Division of Respiratory Disease, Department of Internal Medicine, The Second Xiangya Hospital, Central-South University, No. 139 Middle Renmin Road, Changsha, 410011, Hunan, China. chenyan727@yahoo.com
Yan
Y
Chen
Hong
H
Luo
Naixin
N
Kang
Chaxiang
C
Guan
Yingjiao
Y
Long
Jun
J
Cao
Qin
Q
Shen
Junli
J
Li
Min
M
Yang
Hong
H
Peng
Ping
P
Chen
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016022:Case-Control Studies; D053148:Caspase 3 / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000473:pathology; D051381:Rats; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
C048081:beraprost; D015121:6-Ketoprostaglandin F1 alpha; D003577:Cytochrome P-450 Enzyme System; D011464:Epoprostenol; D000242:Cyclic AMP; D053148:Caspase 3; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase