Unveiling the cardiovascular impact of Zika Virus: Myocardial injury, prothrombotic state, and oxidative stress in immunocompetent mice.

The Zika virus (ZIKV) has been associated with neurological and cardiovascular complications, including myocarditis, arrhythmias and thrombotic events. This study evaluated the thrombotic and oxidative responses induced by ZIKV in cardiac cells and immunocompetent mice. Cardiac (H9c2) and vascular s...

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Main Authors: Fernanda Marques da Silva, Rafael Aguiar Marschner, Markus Berger, Thais Fumaco Teixeira, Ana Paula Muterle, Letícia Rodrigues, Rafael Teixeira Ribeiro, Paulo Michel Roehe, Diogo Onofre Souza, Carlos Alberto Saraiva Gonçalves, Patrícia Sesterheim
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-07-01
Series:PLoS Neglected Tropical Diseases
Online Access:https://doi.org/10.1371/journal.pntd.0013292
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author Fernanda Marques da Silva
Rafael Aguiar Marschner
Markus Berger
Thais Fumaco Teixeira
Ana Paula Muterle
Letícia Rodrigues
Rafael Teixeira Ribeiro
Paulo Michel Roehe
Diogo Onofre Souza
Carlos Alberto Saraiva Gonçalves
Patrícia Sesterheim
author_facet Fernanda Marques da Silva
Rafael Aguiar Marschner
Markus Berger
Thais Fumaco Teixeira
Ana Paula Muterle
Letícia Rodrigues
Rafael Teixeira Ribeiro
Paulo Michel Roehe
Diogo Onofre Souza
Carlos Alberto Saraiva Gonçalves
Patrícia Sesterheim
author_sort Fernanda Marques da Silva
collection DOAJ
description The Zika virus (ZIKV) has been associated with neurological and cardiovascular complications, including myocarditis, arrhythmias and thrombotic events. This study evaluated the thrombotic and oxidative responses induced by ZIKV in cardiac cells and immunocompetent mice. Cardiac (H9c2) and vascular smooth muscle (A7r5) cell lines were infected with ZIKV and analyzed for viral replication, cytopathic effects and oxidative stress. In vivo, female FVB/N mice were inoculated with ZIKV and cardiac tissue was analyzed for markers of myocardial damage, prothrombotic enzymes and oxidative stress. H9c2 cells demonstrated higher viral replication and cytopathic effects than A7r5 cells. ZIKV-infected cells exhibited increased lactate dehydrogenase release and oxidative stress markers, including elevated protein carbonylation and reactive oxygen species. In vivo, infected mice displayed significant increases in cardiac troponin T levels, indicative of myocardial injury. Analysis of cardiac tissue revealed elevated thrombin and Factor Xa activities and reduced plasmin, indicating a prothrombotic state. Oxidative stress was marked by increased activities of antioxidant enzymes (GPx, SOD) and reduced glutathione levels, alongside heightened protein oxidation. This study demonstrates that ZIKV infection disrupts cardiovascular homeostasis by inducing myocardial injury, prothrombotic state and oxidative stress. These findings underscore the potential of ZIKV to affect the cardiovascular system beyond its established neurotropism, highlighting the need for further investigation into its systemic impacts.
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spelling doaj-art-d67a3d05048f48a7a2ae0b283c804d682025-08-20T02:55:06ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352025-07-01197e001329210.1371/journal.pntd.0013292Unveiling the cardiovascular impact of Zika Virus: Myocardial injury, prothrombotic state, and oxidative stress in immunocompetent mice.Fernanda Marques da SilvaRafael Aguiar MarschnerMarkus BergerThais Fumaco TeixeiraAna Paula MuterleLetícia RodriguesRafael Teixeira RibeiroPaulo Michel RoeheDiogo Onofre SouzaCarlos Alberto Saraiva GonçalvesPatrícia SesterheimThe Zika virus (ZIKV) has been associated with neurological and cardiovascular complications, including myocarditis, arrhythmias and thrombotic events. This study evaluated the thrombotic and oxidative responses induced by ZIKV in cardiac cells and immunocompetent mice. Cardiac (H9c2) and vascular smooth muscle (A7r5) cell lines were infected with ZIKV and analyzed for viral replication, cytopathic effects and oxidative stress. In vivo, female FVB/N mice were inoculated with ZIKV and cardiac tissue was analyzed for markers of myocardial damage, prothrombotic enzymes and oxidative stress. H9c2 cells demonstrated higher viral replication and cytopathic effects than A7r5 cells. ZIKV-infected cells exhibited increased lactate dehydrogenase release and oxidative stress markers, including elevated protein carbonylation and reactive oxygen species. In vivo, infected mice displayed significant increases in cardiac troponin T levels, indicative of myocardial injury. Analysis of cardiac tissue revealed elevated thrombin and Factor Xa activities and reduced plasmin, indicating a prothrombotic state. Oxidative stress was marked by increased activities of antioxidant enzymes (GPx, SOD) and reduced glutathione levels, alongside heightened protein oxidation. This study demonstrates that ZIKV infection disrupts cardiovascular homeostasis by inducing myocardial injury, prothrombotic state and oxidative stress. These findings underscore the potential of ZIKV to affect the cardiovascular system beyond its established neurotropism, highlighting the need for further investigation into its systemic impacts.https://doi.org/10.1371/journal.pntd.0013292
spellingShingle Fernanda Marques da Silva
Rafael Aguiar Marschner
Markus Berger
Thais Fumaco Teixeira
Ana Paula Muterle
Letícia Rodrigues
Rafael Teixeira Ribeiro
Paulo Michel Roehe
Diogo Onofre Souza
Carlos Alberto Saraiva Gonçalves
Patrícia Sesterheim
Unveiling the cardiovascular impact of Zika Virus: Myocardial injury, prothrombotic state, and oxidative stress in immunocompetent mice.
PLoS Neglected Tropical Diseases
title Unveiling the cardiovascular impact of Zika Virus: Myocardial injury, prothrombotic state, and oxidative stress in immunocompetent mice.
title_full Unveiling the cardiovascular impact of Zika Virus: Myocardial injury, prothrombotic state, and oxidative stress in immunocompetent mice.
title_fullStr Unveiling the cardiovascular impact of Zika Virus: Myocardial injury, prothrombotic state, and oxidative stress in immunocompetent mice.
title_full_unstemmed Unveiling the cardiovascular impact of Zika Virus: Myocardial injury, prothrombotic state, and oxidative stress in immunocompetent mice.
title_short Unveiling the cardiovascular impact of Zika Virus: Myocardial injury, prothrombotic state, and oxidative stress in immunocompetent mice.
title_sort unveiling the cardiovascular impact of zika virus myocardial injury prothrombotic state and oxidative stress in immunocompetent mice
url https://doi.org/10.1371/journal.pntd.0013292
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