Visfatin-induced expression of inflammatory mediators in human endothelial cells through the NF-B pathway

W. J. Lee, C. S. Wu, H. Lin, I. T. Lee, C. M. Wu, J. J. Tseng, M. M. Chou, W. H H Sheu

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75 Scopus citations

Abstract

Background: Visfatin is an adipokine that is highly expressed in visceral fat. Plasma levels of visfatin have been reported to be higher in subjects with obesity and/or type 2 diabetes mellitus. However, the role of visfatin in endothelial dysfunction has been largely unexplored. Objectives: We investigated the possible pathogenic role of visfatin in endothelial dysfunction, particularly focusing on its effect on inflammatory mediators. Design: Primary human umbilical vein endothelial cells (HUVECs) pretreated with visfatin (1, 10 and 50 ng ml 1) were used to study the relationship between visfatin and endothelium dysfunction. Expressions of adhesion molecules (ICAM-1, VCAM-1 and E-selectin) and cytokines (interleukin (IL)-6 and IL-8) affected by visfatin were investigated by enzyme-linked immunosorbent assay, flow cytometry and real-time PCR. Activity of nuclear factor (NF)-B was examined by electrophoretic mobility shift assay. Results: At a visfatin concentration of 50 ng ml 1, significant increases in IL-6, IL-8, ICAM-1, VCAM-1 and E-selectin gene expression along with increased IL-6, IL-8 and sE-selectin protein levels in the conditioned medium were detected. Flow cytometry showed that the addition of visfatin significantly increased ICAM-1 expression and VCAM-1 expression (10 and 50 ng ml 1, respectively). Electrophoretic mobility shift assay confirmed that visfatin increased the DNA-binding activity of NF-B. In addition, pretreatment with visfatin (10 and 50 ng ml 1) increased human monocyte cell line THP-1 adhesion to HUVECs. Conclusions: Our findings suggest that visfatin causes endothelial dysfunction by increasing inflammatory and adhesion molecule expression at least partly through the upregulation of NF-B activity.

Original languageEnglish (US)
Pages (from-to)465-472
Number of pages8
JournalInternational Journal of Obesity
Volume33
Issue number4
DOIs
Publication statusPublished - Apr 2009

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Keywords

  • Adhesion
  • Endothelial cell
  • Inflammation
  • Visfatin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics
  • Endocrinology, Diabetes and Metabolism

Cite this

Lee, W. J., Wu, C. S., Lin, H., Lee, I. T., Wu, C. M., Tseng, J. J., ... Sheu, W. H. H. (2009). Visfatin-induced expression of inflammatory mediators in human endothelial cells through the NF-B pathway. International Journal of Obesity, 33(4), 465-472. https://doi.org/10.1038/ijo.2009.24