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Mobilization of Endothelial Progenitors by Recurrent Bacteremias with a Periodontal Pathogen

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  • Moritz Kebschull
  • Manuela Haupt
  • Søren Jepsen
  • James Deschner
  • Georg Nickenig
  • Nikos Werner

Abstract

Background: Periodontal infections are independent risk factors for atherosclerosis. However, the exact mechanisms underlying this link are yet unclear. Here, we evaluate the in vivo effects of bacteremia with a periodontal pathogen on endothelial progenitors, bone marrow-derived cells capable of endothelial regeneration, and delineate the critical pathways for these effects. Methods: 12-week old C57bl6 wildtype or toll-like receptor (TLR)-2 deficient mice were repeatedly intravenously challenged with 109 live P. gingivalis 381 or vehicle. Numbers of Sca1+/flk1+ progenitors, circulating angiogenic cells, CFU-Hill, and late-outgrowth EPC were measured by FACS/culture. Endothelial function was assessed using isolated organ baths, reendothelization was measured in a carotid injury model. RANKL/osteoprotegerin levels were assessed by ELISA/qPCR. Results: In wildtype mice challenged with intravenous P.gingivalis, numbers of Sca1+/flk1+ progenitors, CAC, CFU-Hill, and late-outgrowth EPC were strongly increased in peripheral circulation and spleen, whereas Sca1+/flk1+ progenitor numbers in bone marrow decreased. Circulating EPCs were functional, as indicated by improved endothelial function and improved reendothelization in infected mice. The osteoprotegerin/RANKL ratio was increased after P. gingivalis challenge in the bone marrow niche of wildtype mice and late-outgrowth EPC in vitro. Conversely, in mice deficient in TLR2, no increase in progenitor mobilization or osteoprotegerin/RANKL ratio was detected. Conclusion: Recurrent transient bacteremias, a feature of periodontitis, increase peripheral EPC counts and decrease EPC pools in the bone marrow, thereby possibly reducing overall endothelial regeneration capacity, conceivably explaining pro-atherogenic properties of periodontal infections. These effects are seemingly mediated by toll-like receptor (TLR)-2.

Suggested Citation

  • Moritz Kebschull & Manuela Haupt & Søren Jepsen & James Deschner & Georg Nickenig & Nikos Werner, 2013. "Mobilization of Endothelial Progenitors by Recurrent Bacteremias with a Periodontal Pathogen," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-9, January.
  • Handle: RePEc:plo:pone00:0054860
    DOI: 10.1371/journal.pone.0054860
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    1. Peter Libby, 2002. "Inflammation in atherosclerosis," Nature, Nature, vol. 420(6917), pages 868-874, December.
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