title: Functional blockage of EMMPRIN ameliorates atherosclerosis in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Extracellular matrix metalloproteinase inducer (EMMPRIN), a 58-kDa cell surface glycoprotein, has been identified as a key receptor for transmitting cellular signals mediating metalloproteinase activities, as well as inflammation and oxidative stress. Clinical evidence has revealed that EMMPRIN is expressed in human atherosclerotic plaque; however, the relationship between EMMPRIN and atherosclerosis is unclear. To evaluate the functional role of EMMPRIN in atherosclerosis, we treated apolipoprotein E-deficient (ApoE(-/-)) mice with an EMMPRIN function-blocking antibody.
  
  
  RESULTS
  EMMPRIN was found to be up-regulated in ApoE(-/-) mice fed a 12-week high-fat diet in contrast to 12 weeks of normal diet. Administration of a function-blocking EMMPRIN antibody (100 μg, twice per week for 4 weeks) to ApoE(-/-) mice, starting after 12 weeks of high-fat diet feeding caused attenuated and more stable atherosclerotic lesions, less reactive oxygen stress generation on plaque, as well as down-regulation of circulating interleukin-6 and monocyte chemotactic protein-1 in ApoE(-/-) mice. The benefit of EMMPRIN functional blockage was associated with reduced metalloproteinases proteolytic activity, which delayed the circulating monocyte transmigrating into atherosclerotic lesions.
  
  
  CONCLUSIONS
  EMMPRIN antibody intervention ameliorated atherosclerosis in ApoE(-/-) mice by the down-regulation of metalloproteinase activity, suggesting that EMMPRIN may be a viable therapeutic target in atherosclerosis.
authors: Department of Postgraduate, Third Military Medical University, Chongqing 400038, China.
authors: Hong
authors: H
authors: Liu
authors: Li-xia
authors: LX
authors: Yang
authors: Rui-wei
authors: RW
authors: Guo
authors: Guo-Fu
authors: GF
authors: Zhu
authors: Yan-Kun
authors: YK
authors: Shi
authors: Xian-mei
authors: XM
authors: Wang
authors: Feng
authors: F
authors: Qi
authors: Chuan-ming
authors: CM
authors: Guo
authors: Jin-shan
authors: JS
authors: Ye
authors: Zhi-hua
authors: ZH
authors: Yang
authors: Xing
authors: X
authors: Liang
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology* / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000517:prevention & control; D051926:Basigin / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D059305:Diet, High-Fat / Q000009:adverse effects / Q000379:methods; D015536:Down-Regulation / Q000235:genetics; D008297:Male; D045726:Metalloproteases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D059748:Proteolysis; D011897:Random Allocation
chemical_list: D019138:Antibodies, Blocking; D001057:Apolipoproteins E; C497887:Bsg protein, mouse; D051926:Basigin; D045726:Metalloproteases
keywords: Antibody; Atherosclerosis; EMMPRIN; Matrix metalloproteinases