Enterovirus-related activation of the cardiomyocyte mitochondrial apoptotic pathway in patients with acute myocarditis.

Abstract

AIMS:

We examined the impact of enterovirus (EV) cardiac replication activity on the endomyocardial mitochondrial pathway in patients with acute myocarditis.

METHODS AND RESULTS:

Levels of apoptotic cardiomyocytes were determined by TUNEL and ligation-mediated polymerase chain reaction (PCR) assays and EV replication activity was assessed by immunostaining of EV VP1 capsid protein in ventricular myocytes of patients with acute myocarditis (n = 25), and healthy heart controls (n = 15). Ratio of cytosolic/mitochondrial cytochrome c concentrations was determined by ELISA assay, levels of active caspase-9 were determined by western blot analysis and Bax/Bcl2 mRNA ratio was assessed by real-time reverse transcription-polymerase chain reaction (RT-PCR) in the same cardiac tissues. Patients with EV-associated acute myocarditis (n = 15) exhibited a significantly higher number of apoptotic cardiomyocytes than those with non-EV-associated acute myocarditis (n = 10) and controls (n = 15) (P < 0.001). Endomyocardial ratio of cytosolic/mitochondrial cytochrome c concentrations and levels of active caspase-9 protein were significantly increased in EV than in non-EV-related myocarditis patients (P < 0.001). Moreover, Bax/Bcl2 mRNA ratio was significantly increased in EV than in non-EV-related myocarditis patients (P < 0.001).

CONCLUSION:

Our findings evidence an EV-related activation of the cardiomyocyte mitochondrial apoptotic pathway in patients with acute myocarditis. Moreover, our results indicate that this EV-induced pro-apoptotic mechanism could be partly related to an up-regulation of Bax expression, and suggest that inhibition of this cell death process may constitute the basis for novel therapies.

• Authors: Lydie Ventéo, Thomas Bourlet, Fanny Renois, Fatima Douche-Aourik, Jean-François Mosnier, Geoffroy Lorain De la Grand Maison, Michel Pluot, Bruno Pozzetto, Laurent Andreoletti
• Journal: European heart journal (Eur Heart J) Vol. 31 Issue 6 Pg. 728-36 (Mar 2010) ISSN: 1522-9645 [Electronic] England
• PMID: 19933281 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytochromes c'
• DNA, Viral
• RNA, Messenger
• RNA, Viral
• Viral Fusion Proteins
• Caspase 9

Topics

• Adolescent
• Adult
• Apoptosis (physiology)
• Case-Control Studies
• Caspase 9 (metabolism)
• Cell Transformation, Viral
• Cytochromes c' (metabolism)
• DNA, Viral (analysis)
• Enterovirus Infections
• Female
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Mitochondria, Heart (virology)
• Myocarditis (virology)
• Myocardium (metabolism)
• Myocytes, Cardiac (virology)
• RNA, Messenger (metabolism)
• RNA, Viral (analysis)
• Viral Fusion Proteins (metabolism)
• Young Adult