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MDC Researchers Prevent Virus Induced Myocarditis - First Studies in Mice02.04.2009 - (idw) Max-Delbrück-Centrum für Molekulare Medizin (MDC) Berlin-Buch
Life-threatening cardiac arrhythmia can be a consequence of myocarditis - an inflammation of the cardiac muscle that can be caused by the Coxsackievirus. In mice, Dr. Yu Shi, Chen Chen, and Professor Michael Gotthardt of the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now abolished the infection by blocking the receptor which is required for virus entry. "We did not detect a single cardiomyocyte that was infected by the virus. Inflammation of the heart muscle associated with this virus infection did not develop," Dr. Shi said. (Journal of American College of Cardiology, (J Am Coll Cardiol, 2009; 53:1219-1226, doi:10.1016/j.jacc.2008.10.064).*
The receptor used by the Coxsackievirus to infect the heart is the Coxsackie-adenovirus-receptor (CAR). It can be found in the cell membrane of myocardial fibers. Ulrike Lisewski, Dr. Shi, Michael Radke, and Prof. Gotthardt discovered only recently that CAR is necessary for a regular heart beat.
In their current study, the researchers could demonstrate that genetically engineered mice without CAR were protected from cardiac infection caused by the Coxsackievirus. Moreover, the mice did not show any evidence of inflammatory cardiomyopathy. That is why Professor Gotthardt assumes - contrary to previous hypotheses - that the direct effects of the virus infection, and not the autoimmune response, primarily determine the disease process.
This distinction is important in order to develop effective methods for future therapies of viral myocarditis. One therapeutic option could be to use CAR as a drug target and to block this receptor with a pharmacological agent.
"However," Dr. Shi explained, "complete blockage of CAR in mice leads to cardiac arrhythmia." Ultimately, the researchers aim to block the receptor transiently, so that only the virus entry is affected without a permanent effect on the heart beat.
*Cardiac deletion of the Coxsackievirus-adenovirusreceptor abolishes CVB3 infection and prevents myocarditis in vivo
Yu Shi, MD PhD*, Chen Chen, MSc*, Ulrike Lisewski, MSc*, Uta Wrackmeyer, MSc*, Michael Radke, PhD*, Dirk Westermann, MD?, Martina Sauter, DVM?, Carsten Tschöpe, MD?, Wolfgang Poller, MD?, Karin Klingel, MD?, and Michael Gotthardt, MD.*, §
*Neuromuscular and Cardiovascular Cell Biology, Max-Delbrück-Center for Molecular Medicine (MDC), 13122 Berlin-Buch, Germany,
?Department of Cardiology, Campus Benjamin Franklin, D-12200 Berlin, Germany,
?Department of Molecular Pathology, University Hospital Tübingen, D-72076 Tübingen, Germany,
§Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman, Washington, 99164 USA.
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