HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: dc07-1544v1 31/4/758    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Adya, R. Articles by Randeva, H. S. Search for Related Content PubMed PubMed Citation Articles by Adya, R. Articles by Randeva, H. S. Social Bookmarking                What's this?

Nuclear Factor-B Induction by Visfatin in Human Vascular Endothelial Cells

Its role in MMP-2/9 production and activation

From the Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K.

Address correspondence and reprint requests to Dr. Harpal S. Randeva, MBCHB, FRCP, MD, PhD, Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, U.K. E-mail: harpal.randeva{at}warwick.ac.uk

OBJECTIVE—Visfatin is elevated in obesity and type 2 diabetes and is thought to be an inflammatory mediator within atherosclerotic lesions and to induce gelatinase activity. We investigated the activation of nuclear factor-B (NF-B), a well-known proinflammatory transcription factor, by visfatin in endothelial cells.

RESEARCH DESIGN AND METHODS—Human endothelial cells were transfected with pNF-B-Luc plasmid. Using quantitative PCR, Western blot analysis, and gelatin zymography, we studied NF-B signaling in gelatinase-mediated vascular inflammation by visfatin using the NF-B inhibitor BAY 11-7085.

RESULTS—Visfatin significantly increased NF-B transcriptional activity (P < 0.001). We also found a significant inhibition of tumor necrosis factor- (TNF-)-induced NF-B activity by visfatin (P < 0.001). Furthermore, the NF-B inhibitor significantly negated visfatin-induced matrix metalloproteinase (MMP)-2/9 mRNA expression, protein levels, and gelatinolytic activity (P < 0.001).

CONCLUSIONS—Visfatin-induced NF-B signaling in human endothelial cells affects the activation of gelatinases MMP-2 and -9, suggesting an important role of visfatin in the pathogenesis of vascular inflammation in obesity and type 2 diabetes.

Abbreviations: HUVEC, human umbilical vein endothelial cell • MMP, matrix metalloproteinase • NF-B, nuclear factor-B • TNF-, tumor necrosis factor-

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?