1. Diesel exhaust particles impair endothelial progenitor cells, compromise endothelial integrity, reduce neoangiogenesis, and increase atherogenesis in mice.
- Author
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Pöss J, Lorenz D, Werner C, Pavlikova V, Gensch C, Speer T, Alessandrini F, Berezowski V, Kuntz M, Mempel M, Endres M, Böhm M, and Laufs U
- Subjects
- Animals, Apolipoproteins E genetics, Apoptosis drug effects, Atherosclerosis pathology, Blood-Brain Barrier drug effects, Cell Movement drug effects, Cell Separation, Electron Spin Resonance Spectroscopy, Glucose deficiency, Hypoxia pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Spleen cytology, Superoxides metabolism, Air Pollutants toxicity, Atherosclerosis chemically induced, Endothelial Cells drug effects, Endothelium, Vascular drug effects, Neovascularization, Physiologic drug effects, Particulate Matter toxicity, Stem Cells drug effects, Vehicle Emissions toxicity
- 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.
- Published
- 2013
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