BACKGROUND Influenza virus infection triggers acute cardiovascular events. Several studies have demonstrated that influenza A virus infection was associated with immune cell influx and increased production of inflammatory cytokines in the atherosclerotic plaque lesion, but the underlying mechanism for these findings is not clear. METHODS We examined the expression levels of matrix metalloproteinases (MMPs) by influenza A virus infection in human cells using quantitative real-time polymerase chain reaction, Western blot, and human MMP-13 enzyme-linked immunosorbent assay. In an animal study, protein expression in the plaque lesions of apolipoprotein E (ApoE)-deficient mice were analyzed by immunohistochemistry and Western blot. RESULTS We confirmed that MMP-13 was increased in influenza A virus-infected cells. In the aorta of infected ApoE-deficient mice, MMP-13 was increased at 3 days after infection. Immunohistochemical staining results suggested that collagen was degraded in the MMP-13 expression area and that macrophages were the main source of MMP-13 expression. Furthermore, the expression of MMP-13 was regulated by influenza A virus through activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS In this study, we demonstrated that p38 MAPK-mediated MMP-13 expression by influenza A virus infection led to destabilization of vulnerable atherosclerotic plaques in the artery.

中文翻译：

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甲型流感病毒感染会增加动脉粥样硬化斑块中的基质金属蛋白酶-13。

背景技术流感病毒感染触发急性心血管事件。几项研究表明，甲型流感病毒感染与动脉粥样硬化斑块病变中的免疫细胞流入和炎性细胞因子的产生有关，但这些发现的潜在机制尚不清楚。方法我们使用定量实时聚合酶链反应，Western印迹和人MMP-13酶联免疫吸附试验，检测了人类细胞中甲型流感病毒感染后基质金属蛋白酶（MMP）的表达水平。在一项动物研究中，通过免疫组织化学和蛋白质印迹分析了载脂蛋白E（ApoE）缺陷小鼠斑块病变中的蛋白表达。结果我们证实在甲型流感病毒感染的细胞中MMP-13含量增加。在感染的ApoE缺陷小鼠的主动脉中，感染后3天MMP-13升高。免疫组织化学染色结果表明，胶原蛋白在MMP-13表达区域被降解，巨噬细胞是MMP-13表达的主要来源。此外，甲型流感病毒通过激活p38丝裂原激活的蛋白激酶（MAPK）信号通路来调节MMP-13的表达。结论在这项研究中，我们证明了甲型流感病毒感染p38 MAPK介导的MMP-13表达导致动脉中易损动脉粥样斑块的不稳定。甲型流感病毒通过激活p38丝裂原活化蛋白激酶（MAPK）信号通路来调节MMP-13的表达。结论在这项研究中，我们证明了甲型流感病毒感染p38 MAPK介导的MMP-13表达导致动脉中易损动脉粥样斑块的不稳定。甲型流感病毒通过激活p38丝裂原活化蛋白激酶（MAPK）信号通路来调节MMP-13的表达。结论在这项研究中，我们证明了甲型流感病毒感染p38 MAPK介导的MMP-13表达导致动脉中易损动脉粥样斑块的不稳定。