title: Fatty acid binding protein 4 expression in cerebral vascular malformations: implications for vascular remodelling.
abstract: OBJECTIVE
  Arteriovenous malformations (AVM) and cavernous malformations (CM) are the most commonly encountered cerebral vascular malformations, which are dynamic lesions with de novo growth potentials. Postnatal angiogenesis and vasculogenesis have been postulated to play a role in the pathogenesis of these malformations. Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone, which is expressed in a subset of endothelial cells. FABP4 enhances the angiogenic responses of endothelial cells and is not expressed in normal cerebral vasculature. Herein, we investigated the hypothesis that FABP4 expression may be up-regulated in AVM and CM.
  
  
  METHODS
  The abundance of FABP4 expression was analysed by immunohistochemistry on 35 paraffin-embedded AVM and CM sections. FABP4-expressing cells were further characterized by double immunofluorescence using antibodies against various cell-specific markers.
  
  
  RESULTS
  Heterogenous FABP4 expression was detected in 100% AVM and 78% of CM samples. Endothelial cell FABP4 expression was present in 65% and 43% of AVM and CM, respectively. Interestingly, a population of FABP4-positive perivascular cells was detected in 100% of AVM and 86% of CM sections examined. These cells were negative for markers of macrophages and smooth muscle cells, but expressed vimentin, a marker of mesenchymal cells, including fibroblasts.
  
  
  CONCLUSIONS
  FABP4 expression is detected in AVM and CM in a subset of endothelial cells and some perivascular fibroblast-like vimentin-positive cells.
authors.affiliation: Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
authors.forename: Sule
authors.initials: S
authors.lastname: Cataltepe
authors.affiliation: Department of Neurosurgery, University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Meltem Cevik
authors.initials: MC
authors.lastname: Arikan
authors.affiliation: Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Pathology, University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Smith
authors.affiliation: Department of Neurosurgery, University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Oguz
authors.initials: O
authors.lastname: Cataltepe
mesh_terms: D000293:Adolescent; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000378:metabolism; D016543:Central Nervous System Neoplasms / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D042783:Endothelial Cells / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D054079:Vascular Malformations / Q000378:metabolism*; D066253:Vascular Remodeling; D055815:Young Adult
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins
keywords: angiogenesis, arteriovenous malformation; cavernous malformation; cerebral vascular malformations; endothelium; fatty acid binding protein 4; fibroblast