Is Porphyromonas gingivalis Cell Invasion Required for Atherogenesis? Pharmacotherapeutic Implications
Is Porphyromonas gingivalis Cell Invasion Required for Atherogenesis? Pharmacotherapeutic Implications
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DOI：
10.4049/jimmunol.182.3.1584
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发表时间：
2009-02-01
影响因子：
4.4
通讯作者：
Madan, Monika
中科院分区：
文献类型：
--
作者：
Amar, Salomon;Wu, Shou-chieh;Madan, Monika
各种研究表明慢性细菌感染与动脉粥样硬化性心血管疾病之间存在关联。可以侵入内皮细胞的牙龈卟啉单胞菌是一种可能与这些疾病有关的病原体。如果是这样，阻断其侵袭性的抗生素可能会改善动脉粥样硬化斑块的进展。为了探索牙龈卟啉卟啉在炎症和感染相关动脉粥样硬化中的作用，10周龄ApoE（+/-）小鼠被喂食高脂肪饮食或常规饮食。所有小鼠静脉接种活牙龈假单胞菌（381株）50 μ l (10(7) CFU)，每周1次，连续24周；缺乏菌毛的牙龈假单胞菌；或甲硝唑预防牙龈假单胞菌。小鼠在第一次接种24周后被安乐死并进行评估。与注射野生型牙龈卟啉卟啉的ApoE（+/-）小鼠相比，注射DPG3或甲硝唑的ApoE（+/-）小鼠在近端主动脉和主动脉树的动脉粥样硬化病变明显减少。血清淀粉样蛋白A水平，ApoE（+/-）小鼠，同时接受DPG3或甲硝唑治疗前明显低于ApoE（+/-）小鼠单独接受牙龈卟啉卟啉治疗前。血清细胞因子分析显示，注射dpg3和甲硝唑/P后，促炎细胞因子水平均下降。与仅接受牙龈卟啉单胞菌治疗的小鼠相比，无论饮食如何。牙龈卟啉菌侵袭是动脉粥样硬化进展中的一个关键现象。目前的数据为动脉粥样硬化的病理生理途径提供了新的见解，并为旨在减少动脉粥样硬化的新药物干预铺平了道路。免疫学杂志，2009,32(2):1584-1592。
Various studies have demonstrated an association between chronic bacterial infections and atherosclerotic cardiovascular disease. Porphyromonas gingivalis, which can invade endothelial cells, is one pathogen that may link these disorders. If so, antibiotics that block its invasiveness may ameliorate atherosclerotic plaque progression. To explore the role of invasion of P. gingivalis in inflammation- and infection-associated atherosclerosis, 10-wk-old ApoE(+/-) mice were fed either a high fat diet or a regular chow diet. All mice were inoculated i.v., once per week for 24 consecutive wk, with either 50 mu l of live P. gingivalis (strain 381) (10(7) CFU); a fimbria-deficient P. gingivalis; or metronidazole before P. gingivalis. Mice were euthanized and evaluated 24 wk after the first inoculation. ApoE(+/-) mice injected with DPG3 or metronidazole showed significantly fewer atheromatous lesions in the proximal aorta and the aortic tree compared with ApoE(+/-) mice injected with wild-type P. gingivalis for either diet condition. Serum amyloid A levels were significantly lower in ApoE(+/-) mice that received either DPG3 or metronidazole before P. gingivalis than from ApoE(+/-) mice that received P. gingivalis alone. Serum cytokine analysis revealed decreased levels of proinflammatory cytokines in both DPG3-injected and metronidazole/P. gingivalis-treated ApoE(+/-) mice compared with mice receiving only P. gingivalis, irrespective of diet. P. gingivalis invasion is a critical phenomenon in the progression of atherosclerosis. The present data offer new insights into the pathophysiological pathways involved in atherosclerosis and pave the way for new pharmacological interventions aimed at reducing atherosclerosis. The Journal of Immunology, 2009, 182: 1584-1592.