Roth G A, Moser B, Huang S J, Brandt J S, Huang Y, Papapanou P N, Schmidt A M, Lalla E
Department of Surgery, Division of Surgical Science, College of Physicians and Surgeons, New York, NY 10032, USA.
J Thromb Haemost. 2006 Oct;4(10):2256-61. doi: 10.1111/j.1538-7836.2006.02128.x.
Multiple studies have demonstrated a link between periodontal infections and vascular disease. Porphyromonas gingivalis, a major periodontal pathogen, has been shown to adhere to and invade endothelial cells.
In order to dissect mechanisms underlying these observations, we assessed the role of P. gingivalis infection in modulating properties of endothelial cells linked to atherothrombosis.
Primary human aortic endothelial cells (HAEC) were infected with either P. gingivalis 381 or its non-invasive fimbriae-deficient mutant, DPG3. Markers of coagulation and thrombosis were assessed 8 h and 18 h postinfection in cell lysates and supernatants.
Infection with P. gingivalis 381 significantly enhanced tissue factor expression and activity, and suppressed levels of tissue factor pathway inhibitor. Furthermore, P. gingivalis infection decreased levels and activity of tissue plasminogen activator, and enhanced plasminogen activator inhibitor-1 antigen and activity. Consistent with an important role for bacterial adhesion/invasion in this setting, infection with DPG3 failed to induce procoagulant properties in HAEC. Most of the above effects of P. gingivalis 381 were more apparent at the later time point (18 h postinfection). This suggests that P. gingivalis infection, rather than having an immediate and direct effect, might activate pathways that, in turn, trigger endothelial procoagulant mechanisms.
Taken together these data demonstrate for the first time that infection with a periodontal pathogen induces procoagulant responses in HAEC.
多项研究已证实牙周感染与血管疾病之间存在联系。牙龈卟啉单胞菌是一种主要的牙周病原体，已被证明可黏附并侵入内皮细胞。
为了剖析这些观察结果背后的机制，我们评估了牙龈卟啉单胞菌感染在调节与动脉粥样硬化血栓形成相关的内皮细胞特性中的作用。
用人主动脉内皮细胞（HAEC）原代细胞感染牙龈卟啉单胞菌381或其非侵袭性菌毛缺陷突变体DPG3。在感染后8小时和18小时评估细胞裂解物和上清液中的凝血和血栓形成标志物。
牙龈卟啉单胞菌381感染显著增强了组织因子的表达和活性，并抑制了组织因子途径抑制剂的水平。此外，牙龈卟啉单胞菌感染降低了组织纤溶酶原激活物的水平和活性，并增强了纤溶酶原激活物抑制剂-1抗原和活性。与细菌黏附/侵袭在这种情况下的重要作用一致，DPG3感染未能在HAEC中诱导促凝特性。牙龈卟啉单胞菌381的上述大多数作用在后期时间点（感染后18小时）更为明显。这表明牙龈卟啉单胞菌感染可能不是直接产生即时效应，而是激活一些通路，进而触发内皮促凝机制。
这些数据首次表明，牙周病原体感染可诱导HAEC产生促凝反应。
