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.
- heart failure
Data availability statement
All data relevant to the study are included in the article or uploaded as supplementary information.
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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.
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