XXXX induction of tissue factor expression in aortic smooth muscle cells.

@entity4990 @entity8047 @entity5732 @entity4991 @entity455 @entity1441 @entity3459 @entity4286 @entity731 @entity1366
OBJECTIVE: Tissue factor (TF), the @entity3459 cascade, is expressed by cells in @entity731 . @entity4990 ( @entity4991 ) is a component of oxidized lipoproteins and an agent released by activated platelets. The present study investigated whether and how TF expression is regulated by @entity4991 . METHODS AND RESULTS: Northern blotting, Western blotting, and TF activity assays demonstrated that @entity4991 markedly induced TF mRNA, protein, and activity in vascular smooth muscle cells. @entity4991 -induced TF expression is primarily controlled at the transcriptional level. Phosphorylation of @entity8047 ( @entity8047 ) and extracellular signaling-regulated kinases ( @entity1366 ) was rapidly and markedly induced by @entity4991 . @entity8047 inhibitors @entity5732 and @entity4286 blocked both ERK activation and the increase in TF mRNA. In contrast, the specific p38 MAP kinase inhibitor @entity1441 had no effect on @entity4991 -induced TF mRNA increase. The Galpha(i) protein inhibitor, pertussis toxin, abolished @entity4991 -induced phosphorylation of MEKs and ERKs, as well as the induction of TF mRNA. CONCLUSIONS: Our data demonstrate that a Galpha(i) protein and activation of MEKs and ERKs mediate @entity4991 -induced TF expression. Our data suggest that elevated @entity4991 could be a thrombogenic risk factor by upregulating TF expression. These results may have important implications in vascular remodeling and @entity455 .
