title: Adiponectin improves NF-κB-mediated inflammation and abates atherosclerosis progression in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Atherosclerosis is a common pathological basis of cardiovascular disease. Adiponectin (APN) has been shown to have an anti-atherosclerosis effect, and the underlying mechanisms, however, are largely unknown. Nuclear factor κB (NF-κB) has also been regarded as a proatherogenic factor, mainly because of its regulation of a variety of the proinflammatory genes linked to atherosclerosis. It was hypothesized that the inhibitory effects of adiponectin on the atherosclerosis is through the inhibition of NF-κB signaling pathway.
  
  
  METHODS
  We injected adenovirus of Ad-eGFP virus (control group) or the same amount of Ad-APN-eGFP virus (APN group) in ApoE(-/-) mice tail-intravenously. Blood samples and aorta were executed at 0 day, 4, and 8 week of high-fat diet feeding. Histopathological changes of aortic arch root were detected. Levels of TC, TG, HDL-C, LDL-C were measured. Adiponectin and Matrix metalloproteinases-9 (MMP-9) concentration were detected by enzyme-linked immunosorbent assay. Gene and protein levels of adiponectin, eNOS, IL-6, MCP-1,VCAM-1, and other inflammatory factors were determined. Adiponectin, NF-κB p65 in aortic arch root were determined by immunofluorescence and western blot.
  
  
  RESULTS
  Transduction of Ad-APN inhibited the formation of atherosclerotic plaque in aorta when compared with control group. The lesion formation in aortic arch root was inhibited significantly (P < 0.01). Lesion lumen ratio decreased significantly (P < 0.001). The expression of adiponectin attenuated the increases of serum TC (P < 0.001), TG (P < 0.001), and LDL-C (P < 0.001) induced by the high-fat diet, and the increase in body weight (P < 0.05). As increasing serum adiponectin, the levels of MMP-9 were significantly decreased (P < 0.05). The exogenous adiponectin increased the gene expression of the anti-inflammatory factors eNOS (P < 0.05) and IL-10 (P < 0.001), and reduced the gene expression of inflammatory factors tumor necrosis factor-α (TNF-α) (P < 0.001), IL-6 (P < 0.001), VCAM-1 (P < 0.05), respectively. Adiponectin effectively inhibited the activation of NF-κB pathway and the expression of NF-κB nuclear protein p65.
  
  
  CONCLUSIONS
  Adiponectin may protect the aorta from atherosclerotic injury by reducing inflammation. The molecular mechanism may involve inhibited the expression of downstream components of NF-κB and its transcription factors.
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Qingjie
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Science and Research Education Center, First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Pu
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wei
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Duan
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Shou
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Xinjiang Key Laboratory of Medical animal Model Research, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, No.137 South Liyushan Road, Urumqi, 830011, Xinjiang, China. 65242155@qq.com.
authors.forename: Yining
authors.initials: Y
authors.lastname: Yang
mesh_terms: D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology*; D001835:Body Weight / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008817:Mice, Mutant Strains; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001057:Apolipoproteins E; D016328:NF-kappa B; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D020780:Matrix Metalloproteinase 9
keywords: Adiponectin; Atherosclerosis; Inflammation; NF-κB signaling pathways