title: Activation of CD137 signaling accelerates vascular calcification in vivo and vitro.
abstract: OBJECTIVE
  Vascular calcification is a characteristic feature of atherosclerosis and is considered as an independent predictor of cardiovascular risk. CD137 signaling has previously shown to be involved in atherosclerosis. However, the possible role of CD137 signaling in regulation of vascular calcification has not been reported. In the present study, we investigated the effect of CD137 signaling on vascular calcification in ApoE-/-mice and in vascular smooth muscle cells (VSMCs) of mice.
  
  
  METHODS
  Calcium deposition and muscle fibers in vivo or vitro were identified by von-Kossa and Masson's trichrome staining respectively. Alkaline phosphatase (ALP) activity was measured by the ALP assay Kit. The presence of bone morphogenic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) was detected by real-time PCR, Western blot and immunofluorescence in vitro or vivo.
  
  
  RESULTS
  Our data shows that activation of CD137 signaling by intraperitoneal injection of agonist-CD137 antibody increased the areas of vascular calcification. Activation of CD137 signaling also increased the expression of BMP2 and Runx2 in the atherosclerotic plaques. In vitro, activation of CD137 signaling also aggravated VSMC calcification, while blocking CD137 signaling could alleviate agonist-CD137 induced VSMC calcification. In addition, the levels of calcium, BMP2 and Runx2, indicators of calcification, were all significantly elevated in agonist-CD137 group in VSMCs.
  
  
  CONCLUSIONS
  Our data revealed a previously unrecognized role of CD137 signaling in vascular calcification in vivo and vitro and provides a novel target for prevention and treatment of atherosclerosis in the future.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The School of Clinical Medicine, Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China.
authors.forename: Abdul Basit
authors.initials: AB
authors.lastname: Bangash
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Shao
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China.
authors.forename: Zhongqun
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province 212001, PR China. Electronic address: yanjinchuan@hotmail.com.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Yan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D051379:Mice; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000378:metabolism*; D061205:Vascular Calcification / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; C493716:Runx2 protein, mouse; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D012313:RNA; D002118:Calcium
keywords: CD137; Calcification; Osteogenic; TNFRSF; VSMC