title: Blockade of angio-associated migratory cell protein inhibits smooth muscle cell migration and neointima formation in accelerated atherosclerosis.
abstract: OBJECTIVE
  The aim of this study was to elucidate the role of angio-associated migratory cell protein (AAMP) for the migration of vascular smooth muscle cells (SMCs) and for the development of neointimal hyperplasia after vascular injury.
  
  
  BACKGROUND
  Although AAMP has been shown to participate in angiogenesis and cancerogenesis and is predominantly expressed in cells with a migratory phenotype, involvement of AAMP during neointima (NI) formation after arterial injury has not been analyzed previously.
  
  
  METHODS
  The AAMP content in SMCs was examined using 2-photon laser-scanning microscopy and subcellular fractioning. Migratory potential of SMCs transiently transfected with AAMP expression vectors, transfected with small interfering ribonucleic acid (siRNA), or treated with antirecombinant angio-associated migratory cell protein-antibody (anti-rAAMP-ab) was examined using transwell migration chamber assays. Expression of AAMP was determined in the atherogenic apolipoprotein E knockout (apoE(-/-)) mouse model and in the porcine coronary restenosis model by immunohistochemistry and by Western blot. ApoE(-/-) mice were treated intraperitoneally with anti-rAAMP-ab, and wire-injured carotid arteries were examined.
  
  
  RESULTS
  Angio-associated migratory cell protein is localized in the membrane of SMCs, and its expression is enhanced in NI-derived SMCs. The AAMP overexpression increases, while both treatment with anti-rAAMP-ab and transfection with siRNA decreases SMC migration. Knockdown of AAMP decreases RhoA activity in the membrane fraction of SMCs. The AAMP expression by SMCs is enhanced in both animal models. Anti-rAAMP-ab reduces neointimal SMC density at 1 week and NI formation at 4 weeks in apoE(-/-) mice without affecting proliferation of SMCs.
  
  
  CONCLUSIONS
  These data reveal an important functional role of AAMP in the migration of SMCs, identifying AAMP as a potential target to limit lesion formation after injury.
authors.affiliation: Department of Cardiology, RWTH Aachen University, Aachen, Germany.
authors.forename: Felix
authors.initials: F
authors.lastname: Vogt
authors.forename: Alma
authors.initials: A
authors.lastname: Zernecke
authors.forename: Marie
authors.initials: M
authors.lastname: Beckner
authors.forename: Nicole
authors.initials: N
authors.lastname: Krott
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
authors.forename: Rainer
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Marc A M J
authors.initials: MA
authors.lastname: Zandvoort
authors.forename: Thomas
authors.initials: T
authors.lastname: Jahnke
authors.forename: Malte
authors.initials: M
authors.lastname: Kelm
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Blindt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D002352:Carrier Proteins / Q000378:metabolism*; D002465:Cell Movement; D003324:Coronary Artery Disease / Q000209:etiology / Q000503:physiopathology*; D023903:Coronary Restenosis / Q000503:physiopathology; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000098:blood supply* / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D009389:Neovascularization, Pathologic; D011817:Rabbits; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013552:Swine; D017539:Tunica Intima / Q000503:physiopathology*
chemical_list: C093492:AAMP protein, human; D048868:Adaptor Proteins, Signal Transducing; D001057:Apolipoproteins E; D002352:Carrier Proteins; D011947:Receptors, Antigen, B-Cell