Inhibition of endothelial cell migration by cigarette smoke condensate

Cigarette smoking is among the leading risk factors in the etiology of athe rosclerotic 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 f ormation, and after a loss of EC integrity reendothelialization must be rap id 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 cigare tte smoke, individually or in combination, had no effect on migration. Exam ination of the tyrosine phosphorylation state of various intracellular prot eins by Western blot analysis showed that CSC caused the hyperphosphorylati on of a 130-kDa protein. In addition, other intracellular proteins showed c hanges in their phosphorylation states after CSC addition. These results su pport the hypothesis that CSC is detrimental to normal EC function in maint aining vascular integrity and suggest that smokers are more likely to devel op complications of vascular disease due to delayed or incomplete reendothe lialization as a consequence of decreased EC migration. (C) 2001 Academic P ress.