title: CD137-CD137L interaction regulates atherosclerosis via cyclophilin A in apolipoprotein E-deficient mice.
abstract: BACKGROUND
  Our previous studies showed that increased levels of cyclophilin A (CyPA) may be a valuable marker for predicting the severity of acute coronary syndromes and that interruption of CD137-CD137L interactions diminished the formation and progression of atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice. Here, we sought to determine whether the proinflammatory factor CyPA is involved in atherosclerosis regulated by CD137-CD137L interactions.
  
  
  RESULTS
  A constrictive collar was placed around the right carotid arteries of ApoE-/- mice that were fed a high-fat diet to induce atherosclerotic plaque formation. After that, the mice were intraperitoneally injected with anti-CD137 or anti-CD137L in the presence or absence of the recombinant lentiviral vectors LVTHM-CyPA or pGC-FU-CyPA, respectively. Interestingly, activation of CD137-CD137L was negatively correlated with CyPA expression in vivo and in vitro. Stimulating CD137-CD137L interaction significantly increased CyPA, which was concurrent with the upregulation of proinflammatory cytokines, chemokines and matrix metalloproteinases and resulted in the promotion of atherosclerosis in ApoE-/- mice. Silencing CyPA could eliminate these effects, and restoration of CyPA effectively and consistently attenuated the atherosclerotic suppression phenotypes elicited by the blockade of CD137-CD137L.
  
  
  CONCLUSIONS
  These observations suggest that CD137-CD137L interactions mediated via regulation of CyPA contribute to the progression of atherosclerosis.
authors: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China ; Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
authors: Yuefeng
authors: Y
authors: Li
authors: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
authors: Jinchuan
authors: J
authors: Yan
authors: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
authors: Chao
authors: C
authors: Wu
authors: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
authors: Zhongqun
authors: Z
authors: Wang
authors: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
authors: Wei
authors: W
authors: Yuan
authors: Department of Radiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.
authors: Dongqing
authors: D
authors: Wang
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism*; D021984:Cyclophilin A / Q000378:metabolism*; D018450:Disease Progression; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology; D011485:Protein Binding; D015398:Signal Transduction; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism*
chemical_list: D053330:4-1BB Ligand; D001057:Apolipoproteins E; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D021984:Cyclophilin A