Adipocytokine resistin induces tissue factor expression in human coronary artery endothelial cells via NF kB-dependent pathway

Abstract

Objective: Atherosclerosis is characterized by endothelial inflammation and dysfunction. Adipose tissue has been increasingly recognized as an active endocrine organ secreting so-called adipokines, and among them resistin, recently described and not yet extensively studied, has been defined as a novel inflammatory marker in atherosclerosis. The pathophysiology underlying this interplay, however, remains not completely characterized. Aim of the study is to determine whether resistin might affect prothrombotic characteristics of human coronary artery endothelial cells (HCAECs). Methods and results: Incubation of HCAECs with resistin caused up-regulation of the 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 by a colorimetric assay. Resistin-induced TF expression was mediated by oxygen free radicals through the activation of the transcription factor, nuclear factor-kappa B (NF-kB), as demonstrated by electrophoretic mobility shift assay and by suppression of TF expression by superoxide dismutase, catalase, and by NF-kB inhibitors, PDTC and BAY 11-7082. ![Figure][1] Conclusions: These data confirm the hypothesis that resistin may contribute to athero-thrombosis exerting direct effects on HCAECs by promoting TF expression, thus representing an effector molecule able to induce a pro-thrombotic phenotype in cells present in the vessel wall. [1]: pending:yes