Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells.

Abstract

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.

• Authors: Su-Ryun Kim, Yun-Hee Bae, Soo-Kyung Bae, Kyu-Sil Choi, Kwon-Ha Yoon, Tae Hyeon Koo, Hye-Ock Jang, Il Yun, Kyu-Won Kim, Young-Guen Kwon, Mi-Ae Yoo, Moon-Kyoung Bae
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1783 Issue 5 Pg. 886-95 (May 2008) ISSN: 0006-3002 [Print] Netherlands
• PMID: 18241674 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• Reactive Oxygen Species
• Vascular Cell Adhesion Molecule-1
• Intercellular Adhesion Molecule-1
• NADPH Oxidases
• Nicotinamide Phosphoribosyltransferase

Topics

• Cell Adhesion
• Cells, Cultured
• Endothelial Cells (drug effects, metabolism)
• Endothelium, Vascular (cytology, enzymology, metabolism)
• Gene Expression
• Humans
• Intercellular Adhesion Molecule-1 (genetics, metabolism)
• Leukocytes (immunology)
• NADPH Oxidases (metabolism)
• NF-kappa B (metabolism)
• Nicotinamide Phosphoribosyltransferase (pharmacology)
• Promoter Regions, Genetic
• Reactive Oxygen Species (metabolism)
• Vascular Cell Adhesion Molecule-1 (genetics, metabolism)