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 pathwaywith 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 α,β unsaturated aldehyde acrolein, suppressed PGI 2S 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. 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.
|Original language||English (US)|
|Number of pages||10|
|Journal||American journal of respiratory and critical care medicine|
|State||Published - Apr 1 2007|
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine