Calabrò Paolo, Cirillo Plinio, Limongelli Giuseppe, Maddaloni Valeria, Riegler Lucia, Palmieri Rosalinda, Pacileo Giuseppe, De Rosa Salvatore, Pacileo Mario, De Palma Raffaele, Golino Paolo, Calabrò Raffaele
Division of Cardiology, Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy. paolo.calabro @ unina2.it
J Vasc Res. 2011;48(1):59-66. doi: 10.1159/000318775. Epub 2010 Jul 14.
Atherosclerosis is characterized by endothelial inflammation and dysfunction. Adipose tissue has increasingly been recognized as an active endocrine organ secreting so-called adipokines. Among these, resistin--recently described, but not yet extensively studied--has been defined as a novel inflammatory marker in atherosclerosis. The pathophysiology underlying this interplay, however, remains to be fully characterized. The aim of the study is to determine whether resistin might affect prothrombotic characteristics of human coronary artery endothelial cells (HCAECs).
Incubation of HCAECs with resistin caused upregulation of tissue factor (TF) expression as demonstrated by FACS analysis. Moreover, TF activity was induced in a dose-dependent manner, as shown by real-time PCR and colorimetric assay. Resistin-induced TF expression was mediated by oxygen free radicals through the activation of the transcription factor nuclear factor-κB (NF-κB), as demonstrated by electrophoretic mobility shift assay and by suppression of TF expression by superoxide dismutase, catalase, and the NF-κB inhibitors PDTC and BAY 11-7082.
These data confirm the hypothesis that resistin may contribute to atherothrombosis, exerting direct effects on HCAECs by promoting TF expression; thus, it represents an effector molecule able to induce a prothrombotic phenotype in cells present in the vessel wall.
动脉粥样硬化的特征是内皮炎症和功能障碍。脂肪组织越来越被认为是一个分泌所谓脂肪因子的活跃内分泌器官。其中，抵抗素——最近才被描述，但尚未得到广泛研究——已被定义为动脉粥样硬化中的一种新型炎症标志物。然而，这种相互作用背后的病理生理学仍有待充分阐明。本研究的目的是确定抵抗素是否可能影响人冠状动脉内皮细胞（HCAECs）的促血栓形成特性。
用抵抗素孵育人冠状动脉内皮细胞导致组织因子（TF）表达上调，这通过流式细胞术分析得到证实。此外，如实时聚合酶链反应和比色法所示，TF活性以剂量依赖方式被诱导。抵抗素诱导的TF表达由氧自由基通过转录因子核因子-κB（NF-κB）的激活介导，这通过电泳迁移率变动分析以及超氧化物歧化酶、过氧化氢酶和NF-κB抑制剂PDTC和BAY 11-7082对TF表达的抑制得到证实。
这些数据证实了抵抗素可能促成动脉粥样硬化血栓形成的假说，通过促进TF表达对人冠状动脉内皮细胞产生直接影响；因此，它代表了一种能够在血管壁中的细胞中诱导促血栓形成表型的效应分子。
