Cyclophilin A affects inflammation, virus elimination and myocardial fibrosis in coxsackievirus B3-induced myocarditis

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• 作者：Peter Seizer^a ; Karin Klingel^b ; Martina Sauter^b ; Dirk Westermann^c ; Carmen Ochmann^a ; Tanja Sch&ouml ; nberger^a ; Rebecca Schleicher^a ; Konstantinos Stellos^a ; Eva-Maria Schmidt^d ; Oliver Borst^a ; Boris Bigalke^a ; ^e ; Reinhard Kandolf^b ; Harald Langer^a ; Meinrad Gawaz^a ; Andreas E. May^a ; ^{andreas.may@med.uni-tuebingen.de}
• 关键词：Cyclophilin A ; CyPA ; EMMPRIN ; Extracellular Matrix Metalloproteinase Inducer ; CD147 ; MMP ; matrix metalloproteinase ; p.i. ; post infection ; CVB3 ; coxsackievirus B3 ; PPIase ; peptidylprolylisomerase
• 刊名：Journal of Molecular and Cellular Cardiology
• 出版年：2012
• 期刊代码：171_00222828
• 类别：bio
• 出版时间：July, 2012
• 卷：53
• 期：1
• 页码：6-14
• 文件大小：1632 K

摘要

Extracellular cyclophilin A (CyPA) and its receptor Extracellular Matrix Metalloproteinase Inducer (EMMPRIN, CD147) modulate inflammatory processes beyond metalloproteinase (MMP) activity. Recently, we have shown that CyPA and CD147 are upregulated in patients with inflammatory cardiomyopathy. Here we investigate the role of CyPA and CD147 in murine coxsackievirus B3 (CVB3)-induced myocarditis. CVB3-infected CyPA^{鈭?鈭?/sup> mice (129S6/SvEv) revealed a significantly reduced T-cell and macrophage recruitment at 8 days p.i. compared to wild-type mice. In A.BY/SnJ mice, treatment with the cyclophilin-inhibitor NIM811 was associated with a reduction of inflammatory lesions and MMP-9 expression but with enhanced virus replication 8 days p.i. At 28 days p.i. the extent of lesion areas was not affected bei NIM811, whereas the collagen content was reduced. Initiation of NIM811-treatment on day 12 (after an effective virus defense) resulted in an even more pronounced reduction of myocardial fibrosis. In conclusion, in CVB3-induced myocarditis CyPA is important for macrophage and T cell recruitment and effective virus defense and may represent a pharmacological target to modulate myocardial remodeling in myocarditis.}