Cigarette smoke impairs endothelial cell prostacyclin production.
Production of prostacyclin by endothelial cells is considered to be important in rendering the vessel wall nonthrombogenic. Cigarette smoking is an important risk factor in the pathogenesis of atherosclerosis. Here we show that the incubation of cultured human endothelial cells with a cigarette smoke condensate impaired the basal prostacyclin release. Also, the enhanced release of prostacyclin provoked by phorbol myristate acetate was inhibited by cigarette smoke condensate. Furthermore, cigarette smoke condensate impaired the thrombin-induced prostacyclin production. The production of prostacyclin from exogenous arachidonate was not affected by cigarette smoke condensate, indicating that cigarette smoke condensate constituents exert their inhibitory properties on the level of arachidonate mobilization from cellular phospholipids, rather than on cyclooxygenase or prostaglandin synthetase. The effects noted for cigarette smoke condensate could not be attributed to the cigarette smoke constituents nicotine and cadmium. While inhibiting the endothelial cell prostacyclin production significantly, cigarette smoke condensate did not cause cell death or impairment of secretory function, as measured by the release of von Willebrand factor. This in vitro study shows that impairment of an endothelial cell function is related to a risk factor for atherosclerosis.
Reinders
J H
JH
Brinkman
H J
HJ
van Mourik
J A
JA
de Groot
P G
PG
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002104:Cadmium / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D004727:Endothelium / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D006801:Humans; D009538:Nicotine / Q000494:pharmacology; D010947:Plants, Toxic; D011453:Prostaglandins / Q000096:biosynthesis; D012906:Smoke; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014026:Nicotiana; D014841:von Willebrand Factor / Q000378:metabolism
D001095:Arachidonic Acids; D011453:Prostaglandins; D012906:Smoke; D014841:von Willebrand Factor; D002104:Cadmium; D016718:Arachidonic Acid; D000001:Calcimycin; D015121:6-Ketoprostaglandin F1 alpha; D009538:Nicotine; D011464:Epoprostenol; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate