Abstract
BackgroundThe cyclin-dependent kinase inhibitor (CDKI) p27Kip1 regulates cell proliferation and thus inhibits atherosclerosis and vascular remodeling. Expression of tissue factor (TF), the key initator of the coagulation cascade, is associated with atherosclerosis. Yet, it has not been studied whether p27Kip1 influences the expression of TF. Methods and resultsp27Kip1 overexpression in human aortic endothelial cells was achieved by adenoviral transfection. Cells were rendered quiescent for 24h in 0.5% fetal-calf serum. After stimulation with TNF-α (5ng/ml), TF protein expression and activity was significantly reduced (n=4; P<0.001) in cells transfected with p27Kip1. In line with this, p27Kip1 overexpression reduced cytokine-induced TF mRNA expression (n=4; P<0.01) and TF promotor activity (n=4; P<0.05). In contrast, activation of the MAP kinases p38, ERK and JNK was not affected by p27Kip1 overexpression. ConclusionThis in vitro study suggests that p27Kip1 inhibits TF expression at the transcriptional level. These data indicate an interaction between p27Kip1 and TF in important pathological alterations such as atherosclerosis and vascular remodeling.
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