Recent seroepidemiological and immunohistochemical studies have demonstrated an association between microbial infections and atherosclerosis. However, the mechanisms underlying this association are widely unknown. In the present study, arterial specimens obtained at autopsy after sudden death were analyzed concerning (1) the presence of Chlamydia pneumoniae, cytomegalovirus, herpes simplex virus, and Helicobacter pylori; (2) the expression of secretory group IIA phospholipase A(2) (sPLA(2)-IIA) and of proinflammatory cytokines; and (3) the stage of atherosclerosis. Genomic DNA of microbial pathogens was determined by the polymerase chain reaction technique. The expression of sPLA(2)-IIA was studied immunohistochemically by using monoclonal antibodies against human sPLA(2)-IIA. Transcripts specific for sPLA(2)-IIA, interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma were identified by reverse transcription-polymerase chain reaction. In 18 of 102 analyzed specimens, DNA of microbial pathogens was found. Thirteen sections were positive for C pneumoniae, whereas 2 specimens were positive either for cytomegalovirus or for herpes simplex virus. One section contained genomic DNA of all 3 pathogens simultaneously. None of the analyzed tissues exhibited nucleic acids specific for H pylori. In addition to macrophage infiltrates, the presence of microbial DNA was closely associated with the occurrence of transcripts specific for proinflammatory cytokines and sPLA(2)-IIA. Pathogens as well as sPLA(2)-IIA and cytokines were found to be present not only in advanced but also in early stages of atherosclerosis. In tissues negative for sPLA(2)-IIA and cytokine expression, none of the pathogens could be identified. Because macrophages exposed to phospholipase A(2)-treated lipoproteins are transformed into foam cells in vitro, the results of this study suggest an alternative mechanism by which microbial infections may act in a proatherogenic fashion in vessel walls.

译文

最近的血清流行病学和免疫组织化学研究表明,微生物感染与动脉粥样硬化之间存在关联。但是,这种关联的潜在机制尚不清楚。在本研究中,对猝死后尸检获得的动脉标本进行了分析 :( 1) 肺炎衣原体,巨细胞病毒,单纯疱疹病毒和幽门螺杆菌的存在; (2) 分泌型IIA磷脂酶A(2) (sPLA(2)-IIA) 和促炎细胞因子的表达; (3) 动脉粥样硬化的阶段。通过聚合酶链反应技术确定微生物病原体的基因组DNA。通过使用针对人sPLA(2)-IIA的单克隆抗体,免疫组织化学研究了sPLA(2)-IIA的表达。通过逆转录聚合酶链反应鉴定sPLA(2)-IIA,interleukin-1beta,肿瘤坏死因子-α 和干扰素-γ 的特异性转录本。在102个分析标本中的18个中,发现了微生物病原体的DNA。13个切片对肺炎C呈阳性,而2个标本对巨细胞病毒或单纯疱疹病毒呈阳性。一个部分同时包含所有3种病原体的基因组DNA。分析的组织均未显示出对幽门螺杆菌特异性的核酸。除了巨噬细胞浸润外,微生物DNA的存在与促炎细胞因子和sPLA(2)-IIA特异性转录本的发生密切相关。发现病原体以及sPLA(2)-IIA和细胞因子不仅存在于动脉粥样硬化的晚期,而且还存在于动脉粥样硬化的早期。在sPLA(2)-IIA和细胞因子表达阴性的组织中,无法鉴定出任何病原体。由于暴露于磷脂酶A(2) 处理的脂蛋白的巨噬细胞在体外转化为泡沫细胞,因此这项研究的结果表明,微生物感染可能以动脉粥样硬化的方式在血管壁中起作用的另一种机制。

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