Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model.
Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model.
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DOI：
10.3390/v13081588
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发表时间：
2021-08-11
期刊：
影响因子：
--
通讯作者：
Duan G
中科院分区：
文献类型：
--
作者：
Ji W;Zhu P;Liang R;Zhang L;Zhang Y;Wang Y;Zhang W;Tao L;Chen S;Yang H;Jin Y;Duan G
柯萨奇病毒A2 （CVA2）已作为一种活性病原体出现，与世界范围内的手足口病（HFMD）和疱疹性咽峡炎暴发有关。据报道，严重的CVA2感染可发展为心脏损伤，这可能是导致死亡的原因之一。然而，cva2诱导心脏损伤的机制尚不清楚。在这项研究中，我们使用新生小鼠CVA2模型来研究心脏损伤的可能机制。我们检测了感染小鼠心脏组织中CVA2的复制和凋亡。感染小鼠心脏组织中总天冬氨酸转氨酶（AST）和乳酸脱氢酶（LDH）活性显著升高。CVA2感染还导致心脏组织细胞-基质相互作用的破坏，包括基质金属蛋白酶（MMP）3、MMP8、MMP9、结缔组织生长因子（CTGF）和金属蛋白酶组织抑制剂（TIMP）4的升高。感染小鼠心脏组织中可见浸润性白细胞（CD45+和CD11b+细胞）。相应的，CVA2感染小鼠心脏组织裂解物中炎性细胞因子，包括肿瘤坏死因子α (TNF-α)、白细胞介素-1β (IL-1β)、il - 6和单核细胞趋化蛋白-1 （MCP-1）的表达水平显著升高。感染后，心脏组织的炎症信号通路，包括磷脂酰肌醇3-激酶(PI3K)-AKT、丝裂原活化蛋白激酶（MAPK）和核因子κB （NF-κB）也被激活。综上所述，CVA2感染导致新生小鼠模型心脏损伤，这可能与病毒复制、mmp相关酶表达水平升高和过度炎症反应有关。
Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks worldwide. It has been reported that severe cases with CVA2 infection develop into heart injury, which may be one of the causes of death. However, the mechanisms of CVA2-induced heart injury have not been well understood. In this study, we used a neonatal mouse model of CVA2 to investigate the possible mechanisms of heart injury. We detected CVA2 replication and apoptosis in heart tissues from infected mice. The activity of total aspartate transaminase (AST) and lactate dehydrogenase (LDH) was notably increased in heart tissues from infected mice. CVA2 infection also led to the disruption of cell-matrix interactions in heart tissues, including the increases of matrix metalloproteinase (MMP)3, MMP8, MMP9, connective tissue growth factor (CTGF) and tissue inhibitors of metalloproteinases (TIMP)4. Infiltrating leukocytes (CD45+ and CD11b+ cells) were observed in heart tissues of infected mice. Correspondingly, the expression levels of inflammatory cytokines in tissue lysates of hearts, including tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), IL6 and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in CVA2 infected mice. Inflammatory signal pathways in heart tissues, including phosphatidylinositol 3-kinase (PI3K)-AKT, mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB), were also activated after infection. In summary, CVA2 infection leads to heart injury in a neonatal mouse model, which might be related to viral replication, increased expression levels of MMP-related enzymes and excessive inflammatory responses.
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DOI：
10.1016/s1684-1182(10)60016-3
发表时间：
2010-04-01
影响因子：
7.4
作者：
Chen, Shih-Perng;Huang, Yhu-Chering;Lin, Tzou-Yien
通讯作者：
Lin, Tzou-Yien
影响因子：
37.8
作者：
Cheung, Caroline;Marchant, David;McManus, Bruce M.
通讯作者：
McManus, Bruce M.
影响因子：
8.4
作者：
Jan, Sheng-Ling;Lin, Shing-Jong;Hwang, Betau
通讯作者：
Hwang, Betau
影响因子：
4.1
作者：
Becher PM;Gotzhein F;Klingel K;Escher F;Blankenberg S;Westermann D;Lindner D
通讯作者：
Lindner D
影响因子：
3.7
作者：
Cheung, C;Luo, HL;McManus, BM
通讯作者：
McManus, BM