Mobilization of Endothelial Progenitors by Recurrent Bacteremias with a Periodontal Pathogen
Mobilization of Endothelial Progenitors by Recurrent Bacteremias with a Periodontal Pathogen
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DOI：
10.1371/journal.pone.0054860
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发表时间：
2013-01-23
期刊：
影响因子：
3.7
通讯作者：
Werner, Nikos
中科院分区：
文献类型：
--
作者：
Kebschull, Moritz;Haupt, Manuela;Werner, Nikos
背景：牙周感染是动脉粥样硬化的独立危险因素。然而，这种联系背后的确切机制尚不清楚。在这里，我们评估了牙周病原体菌血症对内皮祖细胞（能够内皮再生的骨髓来源细胞）的体内影响，并描绘了这些影响的关键途径。方法：12周龄的C57bl6野生型或Toll样受体（TLR）-2缺陷小鼠反复接受10（9）活P. gingivalis 381或车辆。通过 FACS/培养物测量 Sca1+/flk1+ 祖细胞、循环血管生成细胞、CFU-Hill 和晚期生长 EPC 的数量。使用离体器官浴评估内皮功能，在颈动脉损伤模型中测量再内皮化。通过 ELISA/qPCR 评估 RANKL/骨保护素水平。结果：在接受静脉注射牙龈卟啉单胞菌攻击的野生型小鼠中，外周循环和脾脏中的 Sca1+/flk1+ 祖细胞、CAC、CFU-Hill 和晚期生长 EPC 的数量大幅增加，而骨髓中的 Sca1+/flk1+ 祖细胞数量 减少了。受感染小鼠的内皮功能改善和再内皮化改善表明循环 EPC 具有功能。在野生型小鼠的骨髓生态位和体外晚期生长的 EPC 中，牙龈卟啉单胞菌攻击后，骨保护素/RANKL 比率增加。相反，在TLR2缺陷的小鼠中，没有检测到祖细胞动员或骨保护素/RANKL比值的增加。结论：牙周炎的一个特征，复发性短暂性菌血症，增加外周EPC计数并减少骨髓中的EPC池，从而可能降低整体内皮再生能力，这可以解释牙周炎的促动脉粥样硬化特性。 感染。这些效应似乎是由 Toll 样受体 (TLR)-2 介导的。
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 10(9) 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 proatherogenic properties of periodontal infections. These effects are seemingly mediated by toll-like receptor (TLR)-2.