Fatty acid binding protein 4 expression in cerebral vascular malformations: implications for vascular remodelling

Authors

  • Sule Cataltepe,

    1. Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA
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  • Meltem Cevik Arikan,

    1. Department of Neurosurgery, University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA
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  • Xiaoliang Liang,

    1. Department of Pediatric Newborn Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, USA
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  • Thomas W. Smith,

    1. Department of Pathology, University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA
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  • Oguz Cataltepe

    Corresponding author
    1. Department of Neurosurgery, University of Massachusetts Memorial Medical Center and University of Massachusetts Medical School, Worcester, MA, USA
    • Correspondence: Oguz Cataltepe, Department of Neurosurgery, University of Massachusetts Memorial Medical Center, 55 Lake Avenue North, Suite S2-848, Worcester, MA 01655, USA. Tel: +1 508 334 7667; Fax: +1 508 334 5074; E-mail: oguz.cataltepe@umassmemorial.org

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Abstract

Aim

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.

Conclusion

FABP4 expression is detected in AVM and CM in a subset of endothelial cells and some perivascular fibroblast-like vimentin-positive cells.

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