Inhibition of endothelial cell migration by cigarette smoke condensate.
Cigarette smoking is among the leading risk factors in the etiology of atherosclerotic vascular disease. The mechanism, however, that links cigarette smoking to an increased incidence of atherosclerosis is poorly understood. Endothelial cell (EC) integrity is critical in preventing vascular lesion formation, and after a loss of EC integrity reendothelialization must be rapid and complete. We therefore investigated whether cigarette smoke affected the ECs ability to migrate or altered the intracellular signals generated during migration. The DMSO-soluble fraction of cigarette smoke condensate (CSC), derived from the standard research cigarette, was tested on cultured ECs (HUVEC) derived from human umbilical vein. The addition of CSC caused a dose-dependent decrease in the ability of EC to migrate as measured over a 24-h time period. Nicotine and cadmium sulfate, two constituents of cigarette smoke, individually or in combination, had no effect on migration. Examination of the tyrosine phosphorylation state of various intracellular proteins by Western blot analysis showed that CSC caused the hyperphosphorylation of a 130-kDa protein. In addition, other intracellular proteins showed changes in their phosphorylation states after CSC addition. These results support the hypothesis that CSC is detrimental to normal EC function in maintaining vascular integrity and suggest that smokers are more likely to develop complications of vascular disease due to delayed or incomplete reendothelialization as a consequence of decreased EC migration.
Snajdar
R M
RM
Department of Surgery, Case Western Reserve University Medical School, Cleveland, Ohio 44106, USA.
Busuttil
S J
SJ
Averbook
A
A
Graham
D J
DJ
D001161:Arteriosclerosis / Q000209:etiology* / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology; D014443:Tyrosine / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
D014443:Tyrosine