Necroptosis may be a novel mechanism for cardiomyocyte death in acute myocarditis
In this study, we investigated the roles of RIP1/RIP3 mediated cardiomyocyte necroptosis in CVB3-induced acute myocarditis. Serum concentrations of creatinine kinase (CK), CK-MB, and cardiac troponin I were detected using a Hitachi Automatic Biochemical Analyzer in a mouse model of acute VMC. Histological changes in cardiac tissue were observed by light microscope and expression levels of RIP1/RIP3 in the cardiac tissue were detected via Western blot and immunohistochemistry. The data showed that RIP1/RIP3 was highly expressed in cardiomyocytes in the acute VMC mouse model and that the necroptosis pathway specific blocker, Nec-1, dramatically reduced the myocardial damage by downregulating the expression of RIP1/RIP3. These findings provide evidence that necroptosis plays a significant role in cardiomyocyte death and it is a major pathway for cell death in acute VMC. Blocking the necroptosis pathway may serve as a new therapeutic option for the treatment of acute viral myocarditis.
KeywordsViral myocarditis Coxsackievirus B3 Necroptosis receptor-interacting proteins
The authors would like to thank Cunyu Cao and Hui Zhao for their technical support.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Research involving animals
All procedures, experiments and animal care were approved by the Institutional Animal Care and Use Committees of Wuhan University and conformed to the Guide for the Care and Use of Laboratory Animals by the National Institutes of Health.
- 6.Rosenbaum DM, Degterev A, David J, Rosenbaum PS, Roth S, Grotta JC, Cuny GD, Yuan J, Savitz SI (2010) Necroptosis, a novel form of caspase-independent cell death, contributes to neuronal damage in a retinal ischemia-reperfusion injury model. J Neurosci Res 88(7):1569–1576. doi: 10.1002/jnr.22314 PubMedGoogle Scholar
- 10.Gunther C, Martini E, Wittkopf N, Amann K, Weigmann B, Neumann H, Waldner MJ, Hedrick SM, Tenzer S, Neurath MF, Becker C (2011) Caspase-8 regulates TNF-alpha-induced epithelial necroptosis and terminal ileitis. Nature 477(7364):335–339. doi: 10.1038/nature10400 CrossRefPubMedPubMedCentralGoogle Scholar