Salusin-β not salusin-α promotes vascular inflammation in ApoE-deficient mice via the I-κBα/NF-κB pathway.

OBJECTIVE: Vascular inflammation plays an important role in the development and progression of atherosclerosis. Recently, salusins (salusin-α and salusin-β) have been reported to be associated wtih atherosclerosis. However, its underlying mechanism remains incompletely known. In this study, we observed the effects of salusins on vascular inflammation in apoE-deficient (apoE-/-) mice. METHODS AND RESULTS: Six-week old male apoE-/- mice were infused with salusin-α, salusin-β or vehicle for 8 weeks via osmotic mini-pumps. Our results showed that apoE-/- mice receiving vehicle alone developed severe atherosclerotic lesions and dyslipidemia, with significantly up-regulated levels of IL-6, TNF-α, VCAM-1 and MCP-1. For apoE-/- mice receiving 8 weeks of salusin-β infusion, the atherosclerotic lesions were markedly aggravated, and the levels of IL-6, TNF-α, VCAM-1 and MCP-1 were substantially increased, despite a similar plasma lipid concentration with that of apoE-/- mice. However, after 8 week-infusion of salusin-α, apoE-/- mice presented significant amelioration in atherosclerotic lesions, along with remarkably up-regulated level of high-density lipoprotein-cholesterol (HDL-C) and down-regulated levels of IL-6 and TNF-α, but without any effect on the expressions of VCAM-1 and MCP-1. Furthermore, the activation of nuclear factor-κB (NF-κB), an important transcription factor essential for inflammatory molecules, and the degradation of I-κBα, an inhibitor of NF-κB, were markedly increased in apoE-/- mice receiving vehicle alone. Treatment with salusin-β not salusin-α could remarkably accelerate the process of NF-κB nuclear translocation and I-κBα degradation. CONCLUSION: Salusin-β, but not salusin-α, promotes vascular inflammation in apoE-deficient mice via the I-κBα/NF-κB pathway. These findings provide further insight into the mechanism of salusins in atherosclerosis and potential targets for the prevention and treatment of atherosclerosis