| First Author | Koya T | Year | 2012 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 303 |
| Issue | 1 | Pages | H96-105 |
| PubMed ID | 22561298 | Mgi Jnum | J:189056 |
| Mgi Id | MGI:5444107 | Doi | 10.1152/ajpheart.00009.2012 |
| Citation | Koya T, et al. (2012) Salusin-beta accelerates inflammatory responses in vascular endothelial cells via NF-kappaB signaling in LDL receptor-deficient mice in vivo and HUVECs in vitro. Am J Physiol Heart Circ Physiol 303(1):H96-105 |
| abstractText | 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-1beta and as well as nuclear translocation of NF-kappaB 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-1beta, 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-kappaB, 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-kappaB as well as phosphorylation and degradation of IkappaB-alpha, an endogenous inhibitor of NF-kappaB. Thus, salusin-beta enhanced monocyte adhesion to vascular ECs through NF-kappaB-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. |
