Fatty acid binding protein 4 in circulating leucocytes reflects atherosclerotic lesion progression in Apoe−/− mice

Authors

  • Hanna E Agardh,

    Corresponding author
    • Experimental Cardiovascular Research, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Karl Gertow,

    1. Experimental Cardiovascular Research, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • M. Dolores Salvado,

    1. Division of Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Andreas Hermansson,

    1. Experimental Cardiovascular Research, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Gijs H van Puijvelde,

    1. Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, Leiden, The Netherlands
    Search for more papers by this author
  • Göran K. Hansson,

    1. Experimental Cardiovascular Research, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Gabrielle Paulsson-Berne,

    1. Experimental Cardiovascular Research, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author
  • Anders Gabrielsen

    1. Experimental Cardiovascular Research, Department of Medicine, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
    Search for more papers by this author

Errata

This article is corrected by:

  1. Errata: Corrigendum Volume 17, Issue 6, 815, Article first published online: 20 June 2013

Correspondence to: Hanna AGARDH, PhD, Experimental Cardiovascular Research, CMM L8:03, Karolinska Institute, Karolinska University Hospital, Solna, 171 76 Stockholm, Sweden.

Tel.: +46 (0)8 517 764 06

Fax: +46 (0)8 31 31 47

E-mail: Hanna.agardh@ki.se

Abstract

Discovery of novel biomarkers for atherosclerosis is important to aid in early diagnosis of pre-symptomatic patients at high risk of cardiovascular events. The aim of the present study was therefore to identify potential biomarkers in circulating cells reflecting atherosclerotic lesion progression in the vessel wall. We performed gene arrays on circulating leucocytes from atherosclerosis prone Apoe−/− mice with increasing ages, using C57BL/6 mice as healthy controls. We identified fatty acid binding protein 4 (FABP4) mRNA to be augmented in mice with established disease compared with young Apoe−/− or controls. Interestingly, the transcript FABP4 correlated significantly with lesion size, further supporting a disease associated increase. In addition, validation of our finding on protein level showed augmented FABP4 in circulating leucocytes whereas, importantly, no change could be observed in plasma. Immunofluorescence analysis demonstrated FABP4 to be present mainly in circulating neutrophils and to some extent in monocytes. Moreover, FABP4-positive neutrophils and macrophages could be identified in the subintimal space in the plaque. Using human circulating leucocytes, we confirmed the presence of FABP4 protein in neutrophils and monocytes. In conclusion, we have showed that cellular levels of FABP4 in circulating leucocytes associate with lesion development in the experimental Apoe−/− model. The increased expression is primarily localized to neutrophils, but also in monocytes. We have identified FABP4 in leucocytes as a potential and easy accessible biomarker of atherosclerosis which could be of future clinical relevance.

Ancillary