1. C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation
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Massimo Chiariello, Paolo Golino, Plinio Cirillo, Gaetano Calì, Paolo Calabrò, Lucio Nitsch, Massimo Ragni, Giovanni Cimmino, Fabio Granato Corigliano, Mario Pacileo, Salvatore De Rosa, Raffaele Spagnuolo, Annarita Gargiulo, Valeria Angri, Raffaele De Palma, Lavinia Forte, Cirillo, Plinio, Golino, P, Calabro, P, Cali, G, Ragni, M, De Rosa, S, Cimmino, G, Pacileo, M, De Palma, R, Forte, L, Gargiulo, A, Corigliano, Fg, Angri, V, Spagnuolo, R, Nitsch, Lucio, Chiariello, Massimo, Cirillo, P, Golino, Paolo, Calabro', Paolo, DE ROSA, S, Cimmino, Giovanni, DE PALMA, Raffaele, Nitsch, L, and Chiariello, M.
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MAPK/ERK pathway ,medicine.medical_specialty ,Cell type ,Endothelium ,Physiology ,Inflammation ,Muscle, Smooth, Vascular ,Thromboplastin ,Tissue factor ,c-reactive protein ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Extracellular Signal-Regulated MAP Kinases ,Cells, Cultured ,thrombosis ,Cell Proliferation ,Dose-Response Relationship, Drug ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Cell growth ,NF-kappa B ,Endothelial Cells ,Glyceraldehyde-3-Phosphate Dehydrogenases ,tissue factor ,Stimulation, Chemical ,Up-Regulation ,Cell biology ,Endothelial stem cell ,medicine.anatomical_structure ,Endocrinology ,Mitogen-activated protein kinase ,biology.protein ,Colorimetry ,Endothelium, Vascular ,Rabbits ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Signal Transduction - Abstract
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-kappa B, by CRP was demonstrated by EMSA and by suppression of TF expression by the NF-kappa 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. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
- Published
- 2005
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