Periodontal Pathogen Accelerates Lipid Peroxidation and Atherosclerosis
Periodontal Pathogen Accelerates Lipid Peroxidation and Atherosclerosis
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DOI：
10.1177/0022034513475625
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发表时间：
2013-03-01
影响因子：
7.6
通讯作者：
Yamamoto, M.
中科院分区：
文献类型：
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作者：
Jia, R.;Kurita-Ochiai, T.;Yamamoto, M.
最近的研究表明牙周病和心血管疾病之间存在关联。我们之前报道过，静脉注射放线菌聚集杆菌（Aa）会加速载脂蛋白e缺乏的自发性高脂血症（Apoe(shl)）小鼠的动脉粥样硬化。在这项研究中，我们研究了动脉粥样硬化诱导是否需要活细胞，或者脂多糖（LPS）是否足以增加动脉粥样硬化损伤。小鼠静脉注射活的Aa HK1651，热杀（hk）Aa或Aa LPS，每周3次，连续3周，15周龄时处死。用活Aa、h.k. Aa或Aa LPS治疗的小鼠，动脉粥样硬化斑块覆盖的主动脉窦区域明显大于用载药小鼠。动脉粥样硬化程度依次为活体Aa b> H. K. Aa > Aa LPS > sham。活Aa、h.k. Aa和Aa LPS处理组的Toll和核苷酸寡聚结构域（NOD）样受体mRNA表达显著升高。Aa挑战通过涉及NADPH氧化酶和髓过氧化物酶衍生的活性氧的氧化应激显著促进LDL的氧化。这些结果表明，Aa促进先天免疫信号和低密度脂蛋白（LDL）氧化，并可能促进动脉粥样硬化的发展。
Recent studies have shown an association between periodontal disease and cardiovascular disease. We previously reported that intravenous challenge with Aggregatibacter actinomycetemcomitans (Aa) accelerated atherosclerosis in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice. In this study, we investigated whether live cells were required for atherosclerosis induction or whether lipopolysaccharide (LPS) alone was sufficient to increase atherosclerotic damage. Mice were injected intravenously with live Aa HK1651, heat-killed (H. K.) Aa, or Aa LPS 3 times a week for 3 weeks and were sacrificed at 15 weeks of age. The areas of the aortic sinus that were covered with atherosclerotic plaques were significantly larger in mice treated with live Aa, H. K. Aa, or Aa LPS compared with vehicle-challenged mice. The order of the extent of atherosclerosis was live Aa > H. K. Aa > Aa LPS > sham. Toll and nucleotide oligomerization domain (NOD)-like receptor mRNA expression significantly increased in the live Aa, H. K. Aa, and Aa LPS treatment groups. Aa challenge markedly promoted the oxidation of LDL through oxidative stress involving NADPH oxidase- and myeloperoxidase-derived reactive oxygen species. These results suggested that Aa promoted innate immune signaling and low-density lipoprotein (LDL) oxidation and may facilitate atheroma development.