Vaspin inhibits cytokine-induced nuclear factor-kappa B activation and adhesion molecule expression via AMP-activated protein kinase activation in vascular endothelial cells

Background: Vaspin is an adipocytokine that was recently identified in the visceral adipose tissue of diabetic rats and has anti-diabetic and anti-atherogenic effects. We hypothesized that vaspin prevents inflammatory cytokine-induced nuclear factor-kappa B (NF-kappa B) activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells. Methods: We examined the effects of vaspin on NF kappa B activation and the expression of the NF kappa B-mediated genes intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1 (MCP-1). Human aortic endothelial cells (HAECS) were used. Tumor necrosis factor alpha (TNF alpha) was used as a representative proinflammatory cytokine. Results: Treatment with vaspin significantly increased the phosphorylation of AMPK and acetyl-CoA carboxylase, the down-stream target of AMPK. Furthermore, treatment with vaspin significantly decreased TNF alpha-induced activation of NF-kappa B, as well as the expression of the adhesion molecules ICAM-1, VCAM-1, E-selectin, and MCP-1. These effects were abolished following transfection of AMPK alpha 1-specific small interfering RNA. In an adhesion assay using THP-1 cells, vaspin reduced TNF alpha-induced adhesion of monocytes to HAECS in an AMPK-dependent manner. Conclusions: Vaspin might attenuate the cytokine-induced expression of adhesion molecule genes by inhibiting NF-kappa B following AMPK activation.