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Tissue Factor Is Induced by Resistin in Human Coronary Artery Endothelial Cells by the NF-ĸB-Dependent Pathway

2010; Karger Publishers; Volume: 48; Issue: 1 Linguagem: Inglês

10.1159/000318775

1423-0135

Paolo Calabró, Plinio Cirillo, Giuseppe Limongelli, Valeria Maddaloni, Lucia Riegler, Rosalinda Palmieri, Giuseppe Pacileo, Salvatore De Rosa, Mario Pacileo, Raffaele De Palma, Paolo Golino, Raffaele Calabrò,

Cardiovascular Disease and Adiposity

<i>Objective:</i> 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). <i>Methods and Results:</i> 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-ĸB (NF-ĸB), as demonstrated by electrophoretic mobility shift assay and by suppression of TF expression by superoxide dismutase, catalase, and the NF-ĸB inhibitors PDTC and BAY 11-7082. <i>Conclusions:</i> 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.