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

Abstract

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(-/-) 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.

• Authors: Peter Seizer, Karin Klingel, Martina Sauter, Dirk Westermann, Carmen Ochmann, Tanja Schönberger, Rebecca Schleicher, Konstantinos Stellos, Eva-Maria Schmidt, Oliver Borst, Boris Bigalke, Reinhard Kandolf, Harald Langer, Meinrad Gawaz, Andreas E May
• Journal: Journal of molecular and cellular cardiology (J Mol Cell Cardiol) Vol. 53 Issue 1 Pg. 6-14 (Jul 2012) ISSN: 1095-8584 [Electronic] England
• PMID: 22446162 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ltd. All rights reserved.

Chemical References

• Basigin
• Cyclosporine
• (melle-4)cyclosporin
• Matrix Metalloproteinase 9
• Cyclophilin A

Topics

• Animals
• Basigin (metabolism)
• Cell Line
• Coxsackievirus Infections (immunology)
• Cyclophilin A (antagonists & inhibitors, deficiency, metabolism)
• Cyclosporine (pharmacology)
• Endomyocardial Fibrosis (etiology, immunology, pathology)
• Enterovirus B, Human (immunology)
• Humans
• Macrophages (drug effects, immunology)
• Matrix Metalloproteinase 9 (metabolism)
• Mice
• Mice, 129 Strain
• Mice, Knockout
• Monocytes (drug effects, immunology)
• Myocarditis (complications, immunology, virology)
• T-Lymphocytes (drug effects, immunology)
• Ventricular Remodeling (drug effects)