caa a22 4500 605478724 CHVBK 20210128100407.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s10741-015-9501-z doi (NATIONALLICENCE)springer-10.1007/s10741-015-9501-z Resuscitation of a dead cardiomyocyte [Elektronische Daten] [George Kunkel, Pankaj Chaturvedi, Suresh Tyagi] Although cardiac resuscitation can revive the whole body, the mechanisms are unclear. To this end, we propose that reviving a dead/dysfunctional cardiomyocyte will shed light on resuscitation mechanisms and pave the way to treat cardiac myopathies. The degradation of the myocyte cytoskeleton by the proteasome system which involves calpains, ubiquitin, caspases and matrix metalloproteases is the main focus of this review. The activation of calpains beyond the calpastatin-mediated inhibition due to extensive calcium harbor can lead to titin degradation, damage to the sarcomere and contractile dysfunction. The ubiquitin proteasome system can disturb the protein homeostasis within the cell and generate a dysfunctional myocyte. The matrix metalloproteases disrupt the collagen/elastin ratio and connexins to generate arrhythmias. The concept of cardiac resuscitation stems from protecting the myocyte cytoskeleton and keeping the protein homeostasis intact through management of the degradation machinery. In this regard, proteasome inhibitors for the degradation machinery have an elegant space. Recently exosomes have been identified potentially, as carriers of microRNAs or proteins that can modify the target cells. Exosomes loaded with the inhibitor "cargo” which comprises microRNAs, siRNAs or proteins to inhibit the degradation machinery can be a method of choice for cardiac resuscitation—a process difficult to execute. Springer Science+Business Media New York, 2015 Resuscitation nationallicence Cardiomyocytes nationallicence Calpains nationallicence Ubiquitin nationallicence Proteases nationallicence Homocysteine nationallicence Kunkel George Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, 40202, Louisville, KY, USA aut Chaturvedi Pankaj Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, 40202, Louisville, KY, USA aut Tyagi Suresh Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, 40202, Louisville, KY, USA aut Heart Failure Reviews Springer US; http://www.springer-ny.com 20/6(2015-11-01), 709-719 1382-4147 20:6<709 2015 20 10741 https://doi.org/10.1007/s10741-015-9501-z text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10741-015-9501-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kunkel George Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- Chaturvedi Pankaj Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- Tyagi Suresh Department of Physiology and Biophysics, Health Sciences Centre, A-1216, School of Medicine, University of Louisville, 500, South Preston Street, 40202, Louisville, KY, USA aut NATIONALLICENCE 773 0- Heart Failure Reviews Springer US; http://www.springer-ny.com 20/6(2015-11-01), 709-719 1382-4147 20:6<709 2015 20 10741