title: Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke.
abstract: BACKGROUND
  Impaired endothelial cell-dependent vasodilation, inflammation, apoptosis, and proliferation are manifestations of endothelial dysfunction in chronic obstructive pulmonary disease (COPD). Prostacyclin (PGI(2)) is a major product of the cyclooxygenase pathway with potent vasodilatory and antimitogenic properties and may be relevant to endothelial dysfunction in COPD.
  
  
  OBJECTIVE
  To determine if PGI(2) 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 (PGI(2)S). 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 PGI(2)S overexpression and in vitro studies to determine if PGI(2) expression has protective effects on cigarette smoke-induced endothelial apoptosis.
  
  
  RESULTS
  Human emphysema lung tissue exhibited lower PGI(2)S expression within the pulmonary endothelium than in normal lung. In vitro studies demonstrated that CSE, and in particular the alpha,beta unsaturated aldehyde acrolein, suppressed PGI(2)S 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 PGI(2)S overexpression exhibited less endothelial apoptosis after chronic smoke exposure. In vitro, iloprost exhibited protective effects on CSE-induced apoptosis.
  
  
  CONCLUSIONS
  PGI(2) 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.
authors.affiliation: 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, USA. patrick.nana-sinkam@osumc.edu
authors.forename: S Patrick
authors.initials: SP
authors.lastname: Nana-Sinkam
authors.forename: Jong Deog
authors.initials: JD
authors.lastname: Lee
authors.forename: Sylk
authors.initials: S
authors.lastname: Sotto-Santiago
authors.forename: Robert S
authors.initials: RS
authors.lastname: Stearman
authors.forename: Robert L
authors.initials: RL
authors.lastname: Keith
authors.forename: Qamrul
authors.initials: Q
authors.lastname: Choudhury
authors.forename: Carlyne
authors.initials: C
authors.lastname: Cool
authors.forename: Jane
authors.initials: J
authors.lastname: Parr
authors.forename: Mark D
authors.initials: MD
authors.lastname: Moore
authors.forename: Todd M
authors.initials: TM
authors.lastname: Bull
authors.forename: Norbert F
authors.initials: NF
authors.lastname: Voelkel
authors.forename: Mark W
authors.initials: MW
authors.lastname: Geraci
mesh_terms: D000171:Acrolein / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016022:Case-Control Studies; D018929:Cell Culture Techniques; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D011464:Epoprostenol / Q000502:physiology*; D006801:Humans; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D011656:Pulmonary Emphysema / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control*; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000171:Acrolein; D011464:Epoprostenol