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Interventions are not established. On the basis of the link between inflammation, fibrosis, aldosterone, and extracellular matrix regulation, we aimed to investigate the effect of an early intervention with the mineralocorticoid receptor antagonist (MRA) eplerenone on cardiac remodelling in a murine model of persistent coxsackievirus B3 (CVB3)-induced myocarditis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>SWR\/J mice were infected with 5 \u00d7 104 plaque-forming units of CVB3 (Nancy strain) and daily treated either with eplerenone (200 mg\/kg body weight) or with placebo starting from Day 1. At Day 8 or 28 post infection, mice were haemodynamically characterized and subsequently sacrificed for immunohistological and molecular biology analyses. Eplerenone did not influence CVB3 load. Already at Day 8, 1.8-fold (P &amp;lt; 0.05), 1.4-fold (P &amp;lt; 0.05), 3.2-fold (P &amp;lt; 0.01), and 2.1-fold (P &amp;lt; 0.001) reduction in LV intercellular adhesion molecule 1 expression, presence of monocytes\/macrophages, oxidative stress, and apoptosis, respectively, was observed in eplerenone-treated vs. untreated CVB3-infected mice. In vitro, eplerenone led to 1.4-fold (P &amp;lt; 0.01) and 1.2-fold (P &amp;lt; 0.01) less CVB3-induced cardiomyocyte oxidative stress and apoptosis. Furthermore, collagen production was 1.1-fold (P &amp;lt; 0.05) decreased in cardiac fibroblasts cultured with medium of eplerenone-treated vs. untreated CVB3-infected HL-1 cardiomyocytes. These ameliorations were in vivo translated into prevention of cardiac fibrosis, as shown by 1.4-fold (P &amp;lt; 0.01) and 2.1-fold (P &amp;lt; 0.001) lower collagen content in the LV of eplerenone-treated vs. untreated CVB3-infected mice at Days 8 and 28, respectively. This resulted in an early and long-lasting improvement of LV dimension and function, as indicated by reduced LV end-systolic volume and end-diastolic volume, and an increase in LV contractility (dP\/dtmax) and LV relaxation (dP\/dtmin), respectively (P &amp;lt; 0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early intervention with the MRA eplerenone modulates the acute host and defence reaction and prevents cardiac disease progression in experimental CVB3-induced myocarditis without aggravation of viral load. The findings advocate for an initiation of therapy of viral myocarditis as early as possible, even before the onset of inflammation-induced myocardial dysfunction. This may also have implications for coronavirus disease-19 therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.12887","type":"journal-article","created":{"date-parts":[[2020,7,14]],"date-time":"2020-07-14T12:07:56Z","timestamp":1594728476000},"page":"2838-2852","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Modulation of the Acute Defence Reaction by Eplerenone Prevents Cardiac Disease Progression in Viral Myocarditis"],"prefix":"10.1093","volume":"7","author":[{"given":"Carsten","family":"Tsch\u00f6pe","sequence":"first","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner site Berlin , Berlin ,","place":["Germany"]},{"name":"Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , Campus Virchow Klinikum (CVK), Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Van Linthout","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"J\u00e4ger","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Alexianer Hospital Hedwigsh\u00f6he , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Arndt","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , Campus Benjamin Franklin (CBF), Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Trippel","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , Campus Virchow Klinikum (CVK), Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Elsanhoury","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin , Berlin ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner site Berlin , Berlin ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Rutschow","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology Johanniter-Kliniken , Stendal ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan D.","family":"Anker","sequence":"additional","affiliation":[{"name":"Berlin Institute of Health Center for Regenerative Therapies and Berlin-Brandenburg Center for Regenerative Therapies (BCRT), 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