Nuclear Factor– B Induction by Visfatin in Human Vascular Endothelial Cells: Role in MMP-2/9 Production and Activation

Objective: Visfatin is elevated in obesity and T2DM; and thought to be an inflammatory mediator within atherosclerotic lesions inducing gelatinase activity. We investigated the activation of NFB a well-known pro-inflammatory transcription factor by visfatin in ECs. Research Design and Methods: Human ECs were transfected with pNFB-Luc plasmid. Using Quantitative PCR, western blot analysis and gelatin zymography, we studied NFB signalling in gelatinase mediated vascular inflammation by visfatin; employing the NF-kB inhibitor, BAY 11-7085. Results: Visfatin significantly increased NFB transcriptional activity (P<0.001). Also, we found a significant inhibition of TNFα induced NFB activity by visfatin (P<0.001). Furthermore, the NFB inhibitor, significantly negated visfatin induced MMP-2/9 mRNA expression, protein levels, and gelatinolytic activity (P<0.001). Conclusions: Visfatin induced NFB signalling in human ECs affects the activation of gelatinases-MMP-2/9, suggesting an important role of visfatin in the pathogenesis of vascular inflammation in obesity and T2DM.