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Heart failure and cardiomyopathies
Original research
Dengue virus infection induces inflammation and oxidative stress on the heart
  1. Lucas Miranda Kangussu1,
  2. Vivian Vasconcelos Costa2,
  3. Vania Claudia Olivon3,
  4. Celso Martins Queiroz-Junior3,
  5. Antônio Nei Santana Gondim4,5,
  6. Marcos Barrouin Melo3,
  7. Daniela Reis1,
  8. Natália Nóbrega1,
  9. Natália Araújo1,
  10. Milene Alvarenga Rachid6,
  11. Renan Pedra de Souza7,
  12. Carlos Renato Tirapelli8,
  13. Robson Augusto Souza dos Santos3,
  14. Jader dos Santos Cruz5,
  15. Mauro Martins Teixeira5,
  16. Danielle da Glória de Souza9,
  17. Daniella Bonaventura1
  1. 1 Departamento de Farmacologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
  2. 2 Departamento de Morfologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
  3. 3 Departamento de Fisiologia e Biofísica, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
  4. 4 Departamento de Educação - Campus XII, Universidade do Estado da Bahia, Salvador, Bahia, Brazil
  5. 5 Departamento de Bioquímica e Imunologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
  6. 6 Departamento de Patologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
  7. 7 Departamento de Genética, Ecologia e Evolução, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
  8. 8 Laboratório de Farmacologia, DEPCH, Escola de Enfermagem de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
  9. 9 Departamento de Microbiologia, ICB, Universidade Federal de Minas Gerais, Belo Horizonte, Brasil
  1. Correspondence to Dr Daniella Bonaventura, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; danibona{at}gmail.com

Abstract

Objective Dengue fever is one of the most important arboviral diseases in the world, and its severe forms are characterised by a broad spectrum of systemic and cardiovascular hallmarks. However, much remains to be elucidated regarding the pathogenesis triggered by Dengue virus (DENV) in the heart. Herein, we evaluated the cardiac outcomes unleashed by DENV infection and the possible mechanisms associated with these effects.

Methods A model of an adapted DENV-3 strain was used to infect male BALB/c mice to assess haemodynamic measurements and the functional, electrophysiological, inflammatory and oxidative parameters in the heart.

Results DENV-3 infection resulted in increased systemic inflammation and vascular permeability with consequent reduction of systolic blood pressure and increase in heart rate. These changes were accompanied by a decrease in the cardiac output and stroke volume, with a reduction trend in the left ventricular end-systolic and end-diastolic diameters and volumes. Also, there was a reduction trend in the calcium current density in the ventricular cardiomyocytes of DENV-3 infected mice. Indeed, DENV-3 infection led to leucocyte infiltration and production of inflammatory mediators in the heart, causing pericarditis and myocarditis. Moreover, increased reactive oxygen species generation and lipoperoxidation were also verified in the cardiac tissue of DENV-3 infected mice.

Conclusions DENV-3 infection induced a marked cardiac dysfunction, which may be associated with inflammation, oxidative stress and electrophysiological changes in the heart. These findings provide new cardiac insights into the mechanisms involved in the pathogenesis triggered by DENV, contributing to the research of new therapeutic targets for clinical practice.

  • inflammation
  • pericarditis
  • myocarditis
  • heart failure

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

https://doi.org/10.1136/heartjnl-2020-318912

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    Data availability statement

    All data relevant to the study are included in the article or uploaded as supplementary information.

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    Footnotes

    • LMK and VVC contributed equally.

    • Contributors LMK and VVC: conceptualisation, methodology, investigation, formal analysis and writing and review original draft. VCO: methodology and formal analysis about confocal microscopy. CMQ-J: methodology and formal analysis about histology. ANSG: methodology and formal analysis about electrophysiology. MBM: methodology and formal analysis about echocardiography. DR, NN and NA: writing – review and editing. MAR: formal analysis about histology. RPdS: statistical analysis. CRT: writing – review and editing. RASdS: formal analysis about echocardiography. JdSC: methodology and formal analysis about electrophysiology and resources. MMT and DdGdS: methodology, formal analysis and resources about dengue animal model. DB: conceptualisation, supervision, resources, funding acquisition, writing – review and editing.

    • Funding The present study received support from Instituto Nacional de Ciência e Tecnologia em Dengue (INCT dengue), which is a programme sponsored by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil), Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, Brazil) (grant numbers CBB - APQ-01 267–10) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil) (grant numbers 474923/2012–6).

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.