Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke

S. Patrick Nana-Sinkam, Deog Lee Jong, Sylk Sotto-Santiago, Robert Stearman, Robert L. Keith, Qamrul Choudhury, Carlyne Cool, Jane Parr, Mark D. Moore, Todd M. Bull, Norbert F. Voelkel, Mark W. Geraci

Research output: Contribution to journalArticle

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Abstract

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 languageEnglish (US)
Pages (from-to)676-685
Number of pages10
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume175
Issue number7
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

Fingerprint

Epoprostenol
Smoke
Tobacco Products
Endothelial Cells
Apoptosis
Lung
Chronic Obstructive Pulmonary Disease
Eicosanoids
Emphysema
Aldehydes
Cytosolic Phospholipases A2
Iloprost
Acrolein
Prostaglandin-Endoperoxide Synthases
Vasodilation
Lung Diseases
Endothelium
Western Blotting
Smoking
Immunohistochemistry

Keywords

  • Eicosanoids
  • Emphysema
  • Inflammation
  • Vascular

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke. / Nana-Sinkam, S. Patrick; Jong, Deog Lee; Sotto-Santiago, Sylk; Stearman, Robert; Keith, Robert L.; Choudhury, Qamrul; Cool, Carlyne; Parr, Jane; Moore, Mark D.; Bull, Todd M.; Voelkel, Norbert F.; Geraci, Mark W.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 175, No. 7, 01.04.2007, p. 676-685.

Research output: Contribution to journalArticle

Nana-Sinkam, SP, Jong, DL, Sotto-Santiago, S, Stearman, R, Keith, RL, Choudhury, Q, Cool, C, Parr, J, Moore, MD, Bull, TM, Voelkel, NF & Geraci, MW 2007, 'Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke', American Journal of Respiratory and Critical Care Medicine, vol. 175, no. 7, pp. 676-685. https://doi.org/10.1164/rccm.200605-724OC
Nana-Sinkam, S. Patrick ; Jong, Deog Lee ; Sotto-Santiago, Sylk ; Stearman, Robert ; Keith, Robert L. ; Choudhury, Qamrul ; Cool, Carlyne ; Parr, Jane ; Moore, Mark D. ; Bull, Todd M. ; Voelkel, Norbert F. ; Geraci, Mark W. / Prostacyclin prevents pulmonary endothelial cell apoptosis induced by cigarette smoke. In: American Journal of Respiratory and Critical Care Medicine. 2007 ; Vol. 175, No. 7. pp. 676-685.
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AU - Keith, Robert L.

AU - Choudhury, Qamrul

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AU - Parr, Jane

AU - Moore, Mark D.

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