C-Reactive Protein Enhances Tissue Factor Expression by Vascular Smooth Muscle Cells

Abstract

Objective-We examined the impact of C-reactive protein (CRP) on vascular smooth muscle cell (VSMC) expression of tissue factor (TF) and TF pathway inhibitor (TFPI

C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo

“…In addition, CRP also induced TF expression in both cell types in a dose-dependent fashion, exerting its effect at the transcriptional level, as demonstrated by semiquantitative and by real-time PCR. Activation of the transcription factor, NFκb, by CRP was demonstrated by EMSA and they also demonstrated suppression of TF expression by the NFκb inhibitor, pyrrolidine-dithiocarbamate ammonium [12,36]. In rat pouch macrophages, in vivo, we show for the first time that CRP-induced TF is inhibited by inhibitors to p38MAPK and JNK, but not ERK inhibitor.…”

“…Previously, CRP has been shown to mediate its biological effects in endothelial cells and monocyte-macrophages via CD32 and CD64 [3][4][5][10][11][12][24][25][26][27][28]. Thus, we examined the effects of antibodies to CD16, CD32 and CD64 on CRP-induced superoxide anion release and tissue factor activity.…”

“…CRP upregulates tissue factor (TF) activity in monocytes and cultured vascular smooth muscle cells, CRP upregulates PAI-1 and decreases tPA, eNOS and prostacyclin in HAEC [3,5,11,12]. Furthermore, mice carrying the human CRP (HCRP) transgene exhibit accelerated thrombosis after vascular injury [13].…”

“…Human CRP activates complement in rats. Human CRP has been shown to be pro-inflammatory in the rat and increases inducible nitric oxide synthase expression in cytokine-stimulated rat cardiac myocytes, as well as inducible nitric oxide synthase in rat macrophages, and stimulates nuclear factor-κb (NFκb) in rat vascular smooth muscle cells [3,12,16,17]. Also, the Pepys group [18] has shown that a small molecule inhibitor (bis-phosphatidylcholine) to CRP prevents the increase in infarct size following coronary ligation.…”

Increased level of tumor necrosis factor-α in patients with antiphospholipid syndrome: marker not only of inflammation but also of the prothrombotic state

“…Inflammatory reaction is also accompanied by the increase in fibrinogen and C-reactive protein (CRP) blood levels. CRP itself increases TF and decreases TF pathway inhibitor (TFPI) concentrations, what may be important in pathogenesis of arterial thrombosis and myocardial infarction [5]. Of the natural anticoagulants, protein C pathway appears to be the most strongly influenced by inflammation with thrombomodulin (TM) and the endothelial cell protein C receptor (EPCR) being both downregulated by TNF-a [6].…”