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

Koya T, Miyazaki T, Watanabe T, Shichiri M, Atsumi T, Kim-Kaneyama JR, Miyazaki A. Salusin-beta accelerates inflammatory responses in vascular endothelial cells via NF-kappa B signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro. Am J Physiol Heart Circ Physiol 303: H96-H105, 2012; First published May 4, 2012; doi: 10.1152/ajpheart.00009.2012.-The bioactive peptide salusin-beta is highly expressed in human atheromas; additionally, infusion of antiserum against salusin-beta suppresses the development of atherosclerosis in atherogenic mice. This study examined the roles of salusin-beta in vascular inflammation during atherogenesis. Infusion of antiserum against salusin-beta attenuated the induction of VCAM-1, monocyte chemoattractant protein (MCP)-1, and IL-1 beta and as well as nuclear translocation of NF-kappa B 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-beta directly enhances the expression levels of proinflammatory molecules, including VCAM-1, MCP-1, IL-1 beta, and NADPH oxidase 2, as well as THP-1 monocyte adhesion to cultured human umbilical vein ECs (HUVECs). Both salusin-beta-induced VCAM-1 induction and monocyte/HUVEC adhesion were suppressed by pharmacological inhibitors of NF-kappa B, 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-beta, but not with salusin-alpha, accelerated oxidative stress and nuclear translocation of NF-kappa B as well as phosphorylation and degradation of I kappa B-alpha, an endogenous inhibitor of NF-kappa B. Thus, salusin-beta enhanced monocyte adhesion to vascular ECs through NF-kappa B-mediated inflammatory responses in ECs, which can be modified by PI3K or ERK signals. These findings are suggestive of a novel role of salusin-beta in atherogenesis.