Tissue factor is induced by resistin in human coronary artery endothelial cells by the NF-ĸB-dependent pathway.
OBJECTIVE
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).


RESULTS
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.


CONCLUSIONS
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.
Calabrò
Paolo
P
Division of Cardiology, Department of Cardiothoracic Sciences, Second University of Naples, Naples, Italy. paolo.calabro @ unina2.it
Cirillo
Plinio
P
Limongelli
Giuseppe
G
Maddaloni
Valeria
V
Riegler
Lucia
L
Palmieri
Rosalinda
R
Pacileo
Giuseppe
G
De Rosa
Salvatore
S
Pacileo
Mario
M
De Palma
Raffaele
R
Golino
Paolo
P
Calabrò
Raffaele
R
D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D052243:Resistin / Q000378:metabolism* / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D016329:Sp1 Transcription Factor / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism*; D013927:Thrombosis / Q000378:metabolism* / Q000503:physiopathology; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D016328:NF-kappa B; C499624:RETN protein, human; D017382:Reactive Oxygen Species; D052243:Resistin; D016329:Sp1 Transcription Factor; D013925:Thromboplastin