Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells.
Visfatin has recently been identified as a novel visceral adipokine which may be involved in obesity-related vascular disorders. However, it is not known whether visfatin directly contributes to endothelial dysfunction. Here, we investigated the effect of visfatin on vascular inflammation, a key step in a variety of vascular diseases. Visfatin induced leukocyte adhesion to endothelial cells and the aortic endothelium by induction of the cell adhesion molecules, ICAM-1 and VCAM-1. Promoter analysis revealed that visfatin-mediated induction of CAMs is mainly regulated by nuclear factor-kappaB (NF-kappaB). Visfatin stimulated IkappaBalpha phosphorylation, nuclear translocation of the p65 subunit of NF-kappaB, and NF-kappaB DNA binding activity in HMECs. Furthermore, visfatin increased ROS generation, and visfatin-induced CAMs expression and NF-kappaB activation were abrogated in the presence of the direct scavenger of ROS. Taken together, our results demonstrate that visfatin is a vascular inflammatory molecule that increases expression of the inflammatory CAMs, ICAM-1 and VCAM-1, through ROS-dependent NF-kappaB activation in endothelial cells.
Kim
Su-Ryun
SR
School of Dentistry, Pusan National University, Pusan, South Korea.
Bae
Yun-Hee
YH
Bae
Soo-Kyung
SK
Choi
Kyu-Sil
KS
Yoon
Kwon-Ha
KH
Koo
Tae Hyeon
TH
Jang
Hye-Ock
HO
Yun
Il
I
Kim
Kyu-Won
KW
Kwon
Young-Guen
YG
Yoo
Mi-Ae
MA
Bae
Moon-Kyoung
MK
D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
D016328:NF-kappa B; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019255:NADPH Oxidases; D054409:Nicotinamide Phosphoribosyltransferase