Salusin-ß accelerates inflammatory responses in vascular endothelial cells via NF-κB signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro.

ABSTRACT

The bioactive peptide salusin-ß is highly expressed in human atheromas; additionally, infusion of antiserum against salusin-ß suppresses the development of atherosclerosis in atherogenic mice. This study examined the roles of salusin-ß in vascular inflammation during atherogenesis. Infusion of antiserum against salusin-ß attenuated the induction of VCAM-1, monocyte chemoattractant protein (MCP)-1, and IL-1ß and as well as nuclear translocation of NF-κB in aortic endothelial cells (ECs) of LDL receptor-deficient mice, which led to the prevention of monocyte adhesion to aortic ECs. In vitro experiments indicated that salusin-ß directly enhances the expression levels of proinflammatory molecules, including VCAM-1, MCP-1, IL-1ß, and NADPH oxidase 2, as well as THP-1 monocyte adhesion to cultured human umbilical vein ECs (HUVECs). Both salusin-ß-induced VCAM-1 induction and monocyte/HUVEC adhesion were suppressed by pharmacological inhibitors of NF-κB, e.g., Bay 11-7682 and curcumin. Furthermore, the VCAM-1 induction was significantly prevented by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY-294002, whereas it was accelerated by the ERK inhibitor, U-0126. Treatment of HUVECs with salusin-ß, but not with salusin-α, accelerated oxidative stress and nuclear translocation of NF-κB as well as phosphorylation and degradation of IκB-α, an endogenous inhibitor of NF-κB. Thus, salusin-ß enhanced monocyte adhesion to vascular ECs through NF-κB-mediated inflammatory responses in ECs, which can be modified by PI3K or ERK signals. These findings are suggestive of a novel role of salusin-ß in atherogenesis.