牙龈卟啉单胞菌通过中性粒细胞激活参与人类腹主动脉瘤的发病机制。在大鼠中验证概念。

BACKGROUND

Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia.

METHODS AND FINDINGS

Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed.

CONCLUSIONS

Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression.

背景

腹主动脉瘤（AAA）代表了一种特定形式的动脉粥样血栓形成，其中中性粒细胞的蛋白水解活性起着主要作用。我们假设参与 AAA 生长的中性粒细胞募集和激活可能部分源于牙周炎菌血症的反复发作。

方法和发现

我们的结果表明，人类 AAA 中的中性粒细胞激活与腔内血栓中的中性粒细胞细胞外陷阱（NET）形成有关，导致细胞游离 DNA 的释放。人类 AAA 样本中经常含有细菌 DNA（11/16），特别是与慢性牙周炎（一种常见的牙周病形式）有关的最普遍病原体牙龈卟啉单胞菌（Pg）。在 AAA 患者的血浆中发现了反映 NET 存在的 DNA 和针对 Pg 的抗体增加。使用 AAA 大鼠模型，我们证明了反复注射 Pg 促进了动脉瘤的发展，与在人类中观察到的病理特征相似，例如富含中性粒细胞的腔内血栓的持续存在，而在注射盐水的大鼠中未观察到这种情况，在注射盐水的大鼠中观察到了愈合过程。