Published ahead of print on January 25, 2007, doi:10.1164/rccm.200605-724OC
© 2007 American Thoracic Society doi: 10.1164/rccm.200605-724OC
Prostacyclin Prevents Pulmonary Endothelial Cell Apoptosis Induced by Cigarette Smoke1 Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University, Columbus, Ohio; 2 College of Medicine, Gyeongsang National University, Chinju, South Korea; 3 Division of Pulmonary Sciences and Critical Care Medicine and COPD Center, University of Colorado Health Science Center, Denver, Colorado; and 4 Department of Veterans Affairs Medical Center, Denver, Colorado Correspondence and requests for reprints should be addressed to Patrick Nana-Sinkam, M.D., The Ohio State University, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, 201 Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH 43210. E-mail: patrick.nana-sinkam{at}osumc.edu Rationale: Impaired endothelial cell–dependent vasodilation, inflammation, apoptosis, and proliferation are manifestations of endothelial dysfunction in chronic obstructive pulmonary disease (COPD). Prostacyclin (PGI2) is a major product of the cyclooxygenase pathway with potent vasodilatory and antimitogenic properties and may be relevant to endothelial dysfunction in COPD. Objectives: To determine if PGI2 expression is altered in smoking-related lung disease and if it may be protective in COPD-associated endothelial dysfunction. Methods: We evaluated, by immunohistochemistry, Western blotting, and polymerase chain reaction, human emphysema tissue compared with normal tissue for expression of prostacyclin synthase (PGI2S). We examined the effects of cigarette smoke extract (CSE) and aldehyde components on eicosanoid expression in primary human pulmonary microvascular endothelial cells. Finally, we used a murine model of lung-specific PGI2S overexpression and in vitro studies to determine if PGI2 expression has protective effects on cigarette smoke–induced endothelial apoptosis.
Measurements and Main Results: Human emphysema lung tissue exhibited lower PGI2S expression within the pulmonary endothelium than in normal lung. In vitro studies demonstrated that CSE, and in particular the Conclusions: PGI2 has protective effects in the pulmonary vasculature after acute and chronic cigarette smoke exposure. An imbalance in eicosanoid expression may be important to COPD-associated endothelial dysfunction.
Key Words: eicosanoids • emphysema • inflammation • vascular
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unsaturated aldehyde acrolein, suppressed PGI2S gene expression, whereas CSE significantly induced the upstream mediators COX-2 and cytosolic phospholipase A2 in human pulmonary microvascular endothelial cells. Mice with lung-specific PGI2S overexpression exhibited less endothelial apoptosis after chronic smoke exposure. In vitro, iloprost exhibited protective effects on CSE-induced apoptosis. 
