C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation.
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).


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-kappaB, by CRP was demonstrated by EMSA and by suppression of TF expression by the NF-kappaB 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.
Cirillo
Plinio
P
Division of Cardiology, University of Naples Federico II, Italy. paolo.golina@unina2.it
Golino
Paolo
P
Calabrò
Paolo
P
Calì
Gaetano
G
Ragni
Massimo
M
De Rosa
Salvatore
S
Cimmino
Giovanni
G
Pacileo
Mario
M
De Palma
Raffaele
R
Forte
Lavinia
L
Gargiulo
Annarita
A
Corigliano
Fabio Granato
FG
Angri
Valeria
V
Spagnuolo
Raffaele
R
Nitsch
Lucio
L
Chiariello
Massimo
M
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003124:Colorimetry; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism*; D015854:Up-Regulation
D016328:NF-kappa B; D012333:RNA, Messenger; D002097:C-Reactive Protein; D013925:Thromboplastin; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D048049:Extracellular Signal-Regulated MAP Kinases