The atherosclerotic lesions in apoE-/- mice were ameliorated after 8-week infusion of exogenous salusin-a but aggravated when exogenous salusin-b was given. However, the result about salusin-b infusion was inconsistent with the earlier study, which demonstrating that chronic 8-week infusion of salusin-b has no effect on the progression of atherosclerosis in apoE-/- mice. The discrepancy may be due to different ages of experimental mice adopted, which causes the development of atherosclerosis at various stages. Furthermore, no significant difference was found for the levels of plasma TC, TG and LDL-C between the vehicle-treated apoE-/- mice and the salusin-a-treated mice, despite a higher concentration of HDL-C in salusin-a-treated mice than that in apoE-/- mice. Similarly, no significant difference was observed in plasma lipid levels after salusin-b infusion. Our data suggested that the anti-atherosclerotic role of salusin-a may be associated with the elevated level of HDL-C, which consistent with the previous report. In addition, salusin-a has been reported to inhibit foam cell formation, which may be one another mechanism for salusin-a to alleviate atherosclerosis. Atherosclerosis is a complex and multifactorial disease, whose pathogenesis is associated with inflammatory responses. During the progression of atherosclerosis, adhesion molecules like VCAM1 can promote monocyte adhesion to the intimal Epoxomicin Proteasome inhibitor surface. MCP-1 is related to the migration of monocytes into the intima and accumulates in the injured regions in various vascular diseases, such as atherosclerosis. Subintimal monocytes convert into macrophages, which ingest lipids and then become foam cells. These cells and other arterial wall cells can release proinflammatory cytokines like IL-6 and TNF-a. In the current research, the levels of IL-6, TNF-a, MCP-1 and VCAM-1 in apoE-/- mice were significantly increased. Moreover, increases in cytokine levels in patients with atherosclerosis were reported. These findings indicate the presence of an active vascular inflammatory response in atherosclerosis. Meanwhile, the expressions of IL-6, TNF-a, MCP-1 and VCAM-1 were up-regulated in apoE-/- mice treated with salusin-b, indicating that salusin-b could aggravate the progression of atherosclerosis via upregulation of inflammatory molecules. This result is consistent with other studies where salusin-b is reported to directly upregulate the level of VCAM-1 in endothelial cells. In contrast, salusin-a could selectively down-regulate the levels of IL-6 and TNF-a in plasma not MCP-1 and VCAM-1 in the aorta, suggesting little effects of salusin-a on inflammation in atherosclerosis progression. Many genes encoding cytokines, chemokines and adhesion molecules including IL-6, TNF-a, MCP-1 and VCAM-1 are regulated by NF-kB, and greatly contribute to inflammatory responses. Activated NF-kB is present in the atherosclerotic lesions of apoEdeficient mice. In our current study, NF-kB activation and IkBa degradation were remarkably aggregated in apoE-/- mice.