Cirillo Plinio, Golino Paolo, Calabrò Paolo, Calì Gaetano, Ragni Massimo, De Rosa Salvatore, Cimmino Giovanni, Pacileo Mario, De Palma Raffaele, Forte Lavinia, Gargiulo Annarita, Corigliano Fabio Granato, Angri Valeria, Spagnuolo Raffaele, Nitsch Lucio, Chiariello Massimo
Division of Cardiology, University of Naples Federico II, Italy.
Cardiovasc Res. 2005 Oct 1;68(1):47-55. doi: 10.1016/j.cardiores.2005.05.010.
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).
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.
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.
炎症在动脉粥样硬化血栓形成中起关键作用。除作为主要心血管事件的预后标志物外，近期数据表明，C反应蛋白（CRP）可能通过对血管细胞产生直接作用而直接促进动脉粥样硬化血栓形成。本研究的目的是确定CRP是否会影响内皮细胞（ECs）和平滑肌细胞（SMCs）的促血栓形成和增殖特性。
用CRP孵育ECs和SMCs导致细胞增殖呈剂量依赖性激活，这是由p44/42丝裂原活化蛋白激酶（ERK 1/2）途径的激活介导的。此外，CRP还以剂量依赖性方式诱导两种细胞类型中的组织因子（TF）表达，如通过半定量和实时PCR所示，其在转录水平发挥作用。通过电泳迁移率变动分析（EMSA）以及NF-κB抑制剂吡咯烷二硫代氨基甲酸铵对TF表达的抑制，证实了CRP对转录因子NF-κB的激活。
这些数据表明，CRP通过促进增殖和TF表达对ECs和SMCs产生直接作用，并支持以下观点：CRP除了作为炎症标志物外，还是一种能够在血管壁细胞中诱导促动脉粥样硬化血栓形成表型的效应分子。
