Mobilization of Endothelial Progenitors by Recurrent Bacteremias with a Periodontal PathogenReport as inadecuate




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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.



Author: Moritz Kebschull, Manuela Haupt, Søren Jepsen, James Deschner, Georg Nickenig, Nikos Werner

Source: http://plos.srce.hr/



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