title: Salusin-β not salusin-α promotes vascular inflammation in ApoE-deficient mice via the I-κBα/NF-κB pathway.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Cheng-Hua
authors.initials: CH
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Ming-Xing
authors.initials: MX
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Pan
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Xiao-Xing
authors.initials: XX
authors.lastname: Yin
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Teng-Fei
authors.initials: TF
authors.lastname: Ma
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China; Department of Anesthetic Pharmacology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Yu-Qing
authors.initials: YQ
authors.lastname: Wu
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005786:Gene Expression Regulation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; D012333:RNA, Messenger; C478739:TOR2A protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha