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Cardiovascular Toxicology

, Volume 13, Issue 3, pp 290–300 | Cite as

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

  • Janine Pöss
  • Dominik Lorenz
  • Christian Werner
  • Valerie Pavlikova
  • Christoph Gensch
  • Thimoteus Speer
  • Francesca Alessandrini
  • Vincent Berezowski
  • Mélanie Kuntz
  • Martin Mempel
  • Matthias Endres
  • Michael Böhm
  • Ulrich Laufs
Article

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.

Keywords

Basic science Diesel exhaust particles Endothelial progenitor cells 

Notes

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.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Janine Pöss
    • 1
  • Dominik Lorenz
    • 1
  • Christian Werner
    • 1
  • Valerie Pavlikova
    • 1
  • Christoph Gensch
    • 1
  • Thimoteus Speer
    • 2
  • Francesca Alessandrini
    • 3
  • Vincent Berezowski
    • 4
    • 5
  • Mélanie Kuntz
    • 4
    • 5
  • Martin Mempel
    • 6
  • Matthias Endres
    • 7
  • Michael Böhm
    • 1
  • Ulrich Laufs
    • 1
  1. 1.Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische IntensivmedizinUniversitätsklinikum des SaarlandesHomburg, SaarGermany
  2. 2.Klinik für Innere Medizin IV, NephrologieUniversitätsklinikum des SaarlandesHomburg, SaarGermany
  3. 3.Institute of Allergy ResearchHelmholtz Zentrum/Technische Universität München, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), ZAUM Center for Allergy and EnvironmentNeuherberg and MunichGermany
  4. 4.Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE)Université Lille Nord de FranceLilleFrance
  5. 5.Faculté des Sciences Jean PerrinUniversité d’ArtoisLens CedexFrance
  6. 6.Abteilung Dermatologie, Venerologie und AllergologieUniversistätsmedizin GöttingenGöttingenGermany
  7. 7.Klinik und Hochschulambulanz für Neurologie and Center for Stroke Research Berlin CharitéUniversitätsmedizin BerlinBerlinGermany

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