Copyright © 2005, European Society of Cardiology
C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation
aFrom the Division of Cardiology, University of Naples "Federico II", Italy
bDivision of Cardiology, Second University of Naples, Italy
cIEOS "G. Salvatore" - National Council of Research, Naples, Italy
dDepartment of Clinical and Experimental Medicine, Second University of Naples, Italy
eDepartment of Molecular and Cellular Biology and Pathology, University of Naples "Federico II", Naples, Italy
* Corresponding author. Tel.: +39 81 7064050; fax: +39 81 7064275. Email address: paolo.golino{at}unina2.it
Objective: Inflammation plays a pivotal role in atherothrombosis. In addition to being a prognostic marker for major cardiovascular events, recent data indicate that C-reactive protein (CRP) might directly promote atherothrombosis by exerting direct effects on vascular cells. The aim of the present study was to determine whether CRP might affect the prothrombotic and proliferative characteristics of endothelial (ECs) and smooth muscle cells (SMCs).
Methods and results: Incubation of ECs and SMCs with CRP resulted in a dose-dependent activation of cell proliferation, which was mediated by activation of the p44/42 MAP Kinase (ERK 1/2) pathway. In addition, CRP also induced tissue factor (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, NF-
B, by CRP was demonstrated by EMSA and by suppression of TF expression by the NF-B inhibitor, pyrrolidine-dithio-carbamate ammonium.
Conclusions: These data indicate that CRP exerts direct effects on ECs and SMCs by promoting proliferation and TF expression and support the notion that CRP, besides representing a marker of inflammation, is an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the vessel wall.
KEYWORDS C-reactive protein; Tissue factor; Thrombosis; Cell proliferation
Time for primary review 24 days
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