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

• Published in: PloS one 2014-03, Vol.9 (3), p.e91468
• Main Authors: Zhou, Cheng-Hua, Liu, Lian, Liu, Lu, Zhang, Ming-Xing, Guo, Hao, Pan, Jin, Yin, Xiao-Xing, Ma, Teng-Fei, Wu, Yu-Qing
• Format: Article
• Language: English
• Subjects: Anesthesiology; Animals; Aorta - drug effects; Aorta - metabolism; Aorta - pathology; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - deficiency; Arteriosclerosis; Atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - metabolism; Atherosclerosis - pathology; Biology; Cardiovascular disease; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Cholesterol; Coronary vessels; Degradation; Disease Progression; Dyslipidemia; Gene Expression Regulation - drug effects; High density lipoprotein; Hypertension; I-kappa B Proteins - metabolism; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Intercellular Signaling Peptides and Proteins - pharmacology; Interleukin 6; Interleukin-6 - metabolism; Laboratory animals; Lesions; Lipoproteins; Male; Medicine; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein 1; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; NF-κB protein; Nuclear transport; Pharmacy; RNA, Messenger - genetics; RNA, Messenger - metabolism; Rodents; Signal Transduction - drug effects; Studies; Translocation; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vascular cell adhesion molecule 1; Vascular Cell Adhesion Molecule-1 - genetics; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0091468

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. 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. 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.