对侵袭性细菌的天然免疫识别会加速载脂蛋白E缺乏小鼠的动脉粥样硬化。

Innate immune recognition of invasive bacteria accelerates atherosclerosis in apolipoprotein E-deficient mice.

作者信息

Gibson Frank C, Hong Charlie, Chou Hsin-Hua, Yumoto Hiromichi, Chen Jiqiu, Lien Egil, Wong Jodie, Genco Caroline Attardo

机构信息

Department of Medicine, Section of Infectious Diseases, Boston University Medical Center, Boston, Mass, USA.

出版信息

Circulation. 2004 Jun 8;109(22):2801-6. doi: 10.1161/01.CIR.0000129769.17895.F0. Epub 2004 May 3.

Abstract

BACKGROUND

Infectious diseases have emerged as potential risk factors for cardiovascular disease (CVD). Epidemiological studies support a connection between periodontal disease, a chronic inflammatory disease of the supporting tissues of the teeth, and CVD.

METHODS AND RESULTS

To directly test the connection between periodontal disease and atherosclerosis, apoE-/- mice were orally challenged with the periodontal disease pathogen Porphyromonas gingivalis or an invasion-impaired P gingivalis fimbriae-deficient mutant (FimA-). Both wild-type P gingivalis and the FimA- mutant were detected in blood and aortic arch tissue of apoE-/- mice by PCR after challenge. ApoE-/- mice challenged with wild-type P gingivalis presented with increased atherosclerotic plaque and expressed the innate immune response markers Toll-like receptor (TLR)-2 and TLR-4 in aortic tissue. Despite detection of the FimA- mutant in the blood and in aortic arch tissue, apoE-/- mice challenged with the FimA- mutant did not present with periodontal disease, upregulation of TLRs, or accelerated atherosclerosis. Furthermore, we demonstrate that immunization to control P gingivalis-elicited periodontal disease concomitantly prevents P gingivalis-accelerated atherosclerosis.

CONCLUSIONS

We conclude that invasive P gingivalis accelerates atherosclerosis.

摘要

背景

传染病已成为心血管疾病(CVD)的潜在危险因素。流行病学研究支持牙周疾病(一种牙齿支持组织的慢性炎症性疾病)与心血管疾病之间存在联系。

方法与结果

为了直接检测牙周疾病与动脉粥样硬化之间的联系,给载脂蛋白E基因敲除(apoE-/-)小鼠口服牙周疾病病原体牙龈卟啉单胞菌或一种侵袭受损的牙龈卟啉单胞菌菌毛缺陷突变体(FimA-)。攻击后通过聚合酶链反应(PCR)在apoE-/-小鼠的血液和主动脉弓组织中检测到野生型牙龈卟啉单胞菌和FimA-突变体。用野生型牙龈卟啉单胞菌攻击的apoE-/-小鼠出现动脉粥样硬化斑块增加,并在主动脉组织中表达天然免疫反应标志物Toll样受体(TLR)-2和TLR-4。尽管在血液和主动脉弓组织中检测到FimA-突变体,但用FimA-突变体攻击的apoE-/-小鼠未出现牙周疾病、TLR上调或动脉粥样硬化加速。此外,我们证明控制牙龈卟啉单胞菌引起的牙周疾病的免疫接种同时可预防牙龈卟啉单胞菌加速的动脉粥样硬化。

结论

我们得出结论,具有侵袭性的牙龈卟啉单胞菌会加速动脉粥样硬化。

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