Aggregatibacter actinomycetemcomitans accelerates atherosclerosis with an increase in atherogenic factors in spontaneously hyperlipidemic mice
Aggregatibacter actinomycetemcomitans accelerates atherosclerosis with an increase in atherogenic factors in spontaneously hyperlipidemic mice
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DOI：
10.1111/j.1574-695x.2010.00674.x
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发表时间：
2010-07-01
影响因子：
--
通讯作者：
Yamamoto, Masafumi
中科院分区：
文献类型：
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作者：
Zhang, Tao;Kurita-Ochiai, Tomoko;Yamamoto, Masafumi
致龋和牙周病原体被认为是心血管疾病发展的病因学因素。我们评估了牙周病原体伴放线菌聚集杆菌和致龋病原体变形链球菌在载脂蛋白E缺陷型自发性高脂血症（Apoeshl）小鼠动脉粥样硬化发展中的参与。小鼠静脉注射A. actinomycetemcomitans HK1651、S.变形链球菌GS-5或磷酸盐缓冲盐水每周三次，持续3周，并在15周龄时处死。Apoeshl小鼠的主动脉窦被动脉粥样硬化斑块覆盖的面积明显大于A。actinomycetemcomitans与S.变形杆菌或赋形剂攻击的小鼠。伴放线菌聚集杆菌攻击可增加血清超敏C反应蛋白和脂多糖水平。在血液、心脏和脾脏中检测到细菌DNA，但在肝脏中未检测到。此外，血清白细胞介素-6（IL-6）、IL-8、肿瘤坏死因子α和MCP-1水平以及主动脉中Toll样受体（TLR）2、TLR 4、ICAM-1、E-选择素、P-选择素、LOX-1、HSP 60、CCL 19、CCL 21、CCR 7和MCP-1表达显著增加。伴放线菌这些结果提示，系统性感染A.放线菌共生菌通过暴露整个微生物或其产物，随后引发炎症，加速Apoeshl小鼠的动脉粥样硬化。促动脉粥样硬化因子的增加可能解释了A.伴放线菌感染
Cariogenic and periodontal pathogens are thought to be etiological factors in the development of cardiovascular disease. We assessed the involvement of the periodontal pathogen Aggregatibacter actinomycetemcomitans and cariogenic pathogen Streptococcus mutans in the development of atherosclerosis in apolipoprotein E-deficient spontaneously hyperlipidemic (Apoeshl) mice. The mice were treated intravenously with A. actinomycetemcomitans HK1651, S. mutans GS-5, or phosphate-buffered saline three times a week for 3 weeks and killed at 15 weeks of age. The areas of the aortic sinus that were covered with atherosclerotic plaque were significantly larger in Apoeshl mice challenged with A. actinomycetemcomitans compared with S. mutans- or vehicle-challenged mice. Aggregatibacter actinomycetemcomitans challenge increased serum high-sensitive C-reactive protein and lipopolysaccharide levels. Bacterial DNA was detected in the blood, heart, and spleen, but not in the liver. Furthermore, serum interleukin-6 (IL-6), IL-8, tumor necrosis factor alpha, and MCP-1 levels and Toll-like receptor (TLR)2, TLR4, ICAM-1, E-selectin, P-selectin, LOX-1, HSP60, CCL19, CCL21, CCR7, and MCP-1 expressions in the aorta were significantly increased in mice challenged with A. actinomycetemcomitans. These results suggest that systemic infection with A. actinomycetemcomitans accelerates atherosclerosis in Apoeshl mice by exposing the whole microorganisms or their products, followed by initiating inflammation. Increases in proatherogenic factors may explain the aggravation of atherosclerosis by A. actinomycetemcomitans infection.