Unsolved medical issues and new targets for further research in viral myocarditis and dilated cardiomyopathy.
Meaningful advances have been made in understanding the mechanisms that contribute to dilated cardiomyopathy and myocarditis. Our data confirmed the hypothesis that there is an interaction of genetic predisposition and acquired factors, in that both can affect the dystrophin-glycoprotein complex. We could show that dystrophin deficiency increases susceptibility to viral infection. Our experiments addressed the role of coxsackievirus in the pathogenesis of cardiomyopathy, while other viruses may be involved, such as adenovirus, parvovirus, influenza virus, etc. Furthermore, we could demonstrate that cardiac myocyte-specific transgenic expression of SOCS1 inhibited coxsackievirus-induced signaling of Janus kinase (JAK) and signal transducer and activator of transcription (STAT), with accompanying increases in viral replication, cardiomyopathy, and mortality in infected mice. Future treatment strategies may include the development of coxsackie-adenovirus receptor (CAR) inhibitors and enteroviral protease 2A inhibitors. Additional studies are ongoing to determine the effectiveness of these inhibitors on viral infection in culture and in the intact heart.
Knowlton
K U
KU
Department of Medicine, University of California, San Diego School of Medicine, La Jolla 92093, USA. kknowlton@ucsd.edu
D000818:Animals; D009202:Cardiomyopathies / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D016189:Dystrophin / Q000378:metabolism; D004769:Enterovirus Infections / Q000150:complications; D006801:Humans; D053613:Janus Kinase 1; D009205:Myocarditis / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D012307:Risk Factors; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism; D019210:Troponin I / Q000097:blood; D014777:Virus Diseases / Q000150:complications / Q000503:physiopathology / Q000628:therapy
D016189:Dystrophin; D050791:STAT Transcription Factors; D050826:Suppressor of Cytokine Signaling Proteins; D019210:Troponin I; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; D053613:Janus Kinase 1