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.