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Diesel Exhaust Particles Impair Endothelial Progenitor Cells, Compromise Endothelial Integrity, Reduce Neoangiogenesis, and Increase Atherogenesis in Mice

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Abstract

The mechanisms of the harmful cardiovascular effects of small particulate matter are incompletely understood. Endothelial progenitor cells (EPCs) predict outcome of patients with vascular disease. The aim of our study was to examine the effects of diesel exhaust particles (DEP) on EPC and on the associated vascular damage in mice. C57Bl/6 mice were exposed to DEP. 2 μg DEP/day was applicated intranasally for 3 weeks. Exposure to DEP reduced DiLDL/lectin positive EPC to 58.4 ± 5.6 % (p < 0.005). Migratory capacity was reduced to 65.8 ± 3.9 % (p < 0.0001). In ApoE−/− mice, DEP application reduced the number of EPC to 75.6 ± 6.4 % (p < 0.005) and EPC migration to 58.5 ± 6.8 % (p < 0.005). Neoangiogenesis was reduced to 39.5 ± 14.6 % (p < 0.005). Atherogenesis was profoundly increased by DEP treatment (157.7 ± 18.1 % vs. controls, p < 0.05). In cultured human EPC, DEP (0.1–100 μg/mL) reduced migratory capacity to 25 ± 2.6 % (p < 0.001). The number of colony-forming units was reduced to 8.8 ± 0.9 % (p < 0.001) and production of reactive oxygen species was elevated by DEP treatment (p < 0.001). Furthermore, DEP treatment increased apoptosis of EPC (to 266 ± 62 % of control, p < 0.05). In a blood–brain barrier model, DEP treatment impaired endothelial cell integrity during oxygen–glucose deprivation (p < 0.001). Diesel exhaust particles impair endothelial progenitor cell number and function in vivo and in vitro. The reduction in EPC was associated with impaired neoangiogenesis and a marked increase in atherosclerotic lesion formation.

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Acknowledgments

We thank Ellen Becker, Simone Jäger, and Jennifer Franz for their excellent technical assistance. This study was supported by the Deutsche Forschungsgemeinschaft (UL, MB), by the Universität des Saarlandes (HOMFOR, JP), and by the European Stroke Network of the 7th Framework Program.

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Authors and Affiliations

  1. Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Kirrberger Str., 66421, Homburg, Saar, Germany

    Janine Pöss, Dominik Lorenz, Christian Werner, Valerie Pavlikova, Christoph Gensch, Michael Böhm & Ulrich Laufs

  2. Klinik für Innere Medizin IV, Nephrologie, Universitätsklinikum des Saarlandes, 66421, Homburg, Saar, Germany

    Thimoteus Speer

  3. Institute of Allergy Research, Helmholtz Zentrum/Technische Universität München, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), ZAUM Center for Allergy and Environment, Neuherberg and Munich, Germany

    Francesca Alessandrini

  4. Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), Université Lille Nord de France, Lille, France

    Vincent Berezowski & Mélanie Kuntz

  5. Faculté des Sciences Jean Perrin, Université d’Artois, Rue Jean Souvraz, S.P.18, 62307, Lens Cedex, France

    Vincent Berezowski & Mélanie Kuntz

  6. Abteilung Dermatologie, Venerologie und Allergologie, Universistätsmedizin Göttingen, 37075, Göttingen, Germany

    Martin Mempel

  7. Klinik und Hochschulambulanz für Neurologie and Center for Stroke Research Berlin Charité, Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany

    Matthias Endres

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  1. Janine Pöss
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Pöss, J., Lorenz, D., Werner, C. et al. Diesel Exhaust Particles Impair Endothelial Progenitor Cells, Compromise Endothelial Integrity, Reduce Neoangiogenesis, and Increase Atherogenesis in Mice. Cardiovasc Toxicol 13, 290–300 (2013). https://doi.org/10.1007/s12012-013-9208-0

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