Dual roles of calpain in facilitating Coxsackievirus B3 replication and prompting inflammation in acute myocarditis.
Dual roles of calpain in facilitating Coxsackievirus B3 replication and prompting inflammation in acute myocarditis.
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钙蛋白酶在促进柯萨奇病毒 B3 复制和促进急性心肌炎炎症中的双重作用
DOI：
10.1016/j.ijcard.2016.07.121
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发表时间：
2016-10-15
影响因子：
3.5
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Li M;Su Y;Yu Y;Yu Y;Wang X;Zou Y;Ge J;Chen R
病毒性心肌炎（VMC）的治疗一直缺乏有效的方法。我们前期的研究表明钙蛋白酶在VMC发病中的作用。本研究旨在验证钙蛋白酶在柯萨奇病毒B3（CVB 3）诱导的心肌炎治疗中的潜力。本研究引入了一种过表达内源性钙蛋白酶抑制剂钙蛋白酶抑制剂的转基因小鼠。将转基因小鼠和野生型小鼠分别腹腔注射CVB3建立VMC小鼠模型。采用组织学（HE染色和病理分级）和血清学（心肌损伤标志物CK-MB和cTnI）检测心肌损伤。通过病毒衣壳蛋白VP1检测或病毒滴定，观察CVB3在体内和体外的复制。采用免疫印迹或免疫组织化学染色检测MPO、穿孔素、IFN γ、IL 17、Smad 3和MMP 2等炎症/纤维化因子。在划痕试验中研究了钙蛋白酶在调节成纤维细胞迁移中的作用。Calpastatin过表达可显著减轻CVB3感染引起的转基因小鼠心肌损伤，表现为外周血CK-MB和cTnI水平降低，心肌组织学损伤改善。与CVB3感染的野生型小鼠相比，转基因小鼠心脏组织携带的病毒量较低。炎症因子MPO、穿孔素、IFN γ和IL 17表达下调，同时伴有纤维化因子Smad3和MMP 2的抑制。钙蛋白酶在体外参与成纤维细胞的迁移，进一步证明了其在纤维化中的调节作用。Calpain具有促进CVB3复制和促进炎症的双重作用。钙蛋白酶抑制剂对CVB3诱导的心肌炎有明显的治疗作用。钙蛋白酶可能成为临床治疗VMC的新靶点。钙蛋白酶参与心肌炎的病毒复制。钙蛋白酶介导心肌炎的炎症浸润。钙蛋白酶可能是治疗病毒性心肌炎的候选药物。
Viral myocarditis (VMC) treatment has long been lacking of effective methods. Our former studies indicated roles of calpain in VMC pathogenesis. This study aimed at verifying the potential of calpain in Coxsackievirus B3 (CVB3)-induced myocarditis treatment. A transgenic mouse overexpressing the endogenous calpain inhibitor, calpastatin, was introduced in the study. VMC mouse model was established via intraperitoneal injection of CVB3 in transgenic and wild mouse respectively. Myocardial injury was assayed histologically (HE staining and pathology grading) and serologically (myocardial damage markers of CK-MB and cTnI). CVB3 replication was observed in vivo and in vitro via the capsid protein VP1 detection or virus titration. Inflammation/fibrotic factors of MPO, perforin, IFNγ, IL17, Smad3 and MMP2 were evaluated using western blot or immunohistology stain. Role of calpain in regulating fibroblast migration was studied in scratch assays. Calpastatin overexpression ameliorated myocardial injury induced by CVB3 infection significantly in transgenic mouse indicated by reduced peripheral CK-MB and cTnI levels and improved histology injury. Comparing with CVB3-infected wild type mouse, the transgenic mouse heart tissue carried lower virus load. The inflammation factors of MPO, perforin, IFNγ and IL17 were down-regulated accompanied with fibrotic agents of Smad3 and MMP2 inhibition. And calpain participated in the migration of fibroblasts in vitro, which further proves its role in regulating fibrosis. Calpain plays dual roles of facilitating CVB3 replication and inflammation promotion. Calpain inhibition in CVB3-induced myocarditis showed significant treatment effect. Calpain might be a novel target for VMC treatment in clinical practices. Calpain is involved in virus replication in myocarditis. Calpain mediates inflammation infiltration in myocarditis. Calpain might be a candidate for viral myocarditis treatment.
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DOI：
10.1523/jneurosci.1042-10.2010
发表时间：
2010-10-20
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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发表时间：
2012-11
期刊：
Hypertension (Dallas, Tex. : 1979)
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DOI：
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发表时间：
2016-04-01
影响因子：
4.9
作者：
Blanc, Fany;Furio, Laetitia;Si-Tahar, Mustapha
通讯作者：
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影响因子：
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