ArticleJournal of the American College of Cardiology2013
Protease-activated receptor-2 regulates the innate immune response to viral infection in a coxsackievirus B3-induced myocarditis.
Article in Journal of the American College of Cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 68 citations in OpenAlex.
- Proteinase-Activated Receptor 2 (PAR2) Deficiency and Cardiovascular Regulation: Context-Dependent Effects on Inflammation and Fibrosis.Current issues in molecular biology · 2026Review
- Extracellular Vesicles Released by Picornavirus-Infected Cells Modify Antiviral Immune Cell Responses.Journal of extracellular vesicles · 2026Article
- The role of interferon-mediated suppression of monocyte immunothrombosis in infection susceptibility in systemic lupus erythematosus.Clinical and experimental immunology · 2026Article
- STAT3 Increases CVB3 Replication and Acute Pancreatitis and Myocarditis Pathology via Impeding Nuclear Translocation of STAT1 and Interferon-Stimulated Gene Expression.International journal of molecular sciences · 2024Article
- Discovery of a novel ROS-based signature for predicting prognosis and immunosuppressive tumor microenvironment in lung adenocarcinoma.Journal of Cancer · 2024Article
- Review
- Review
- Role of Coxsackievirus B3-Induced Immune Responses in the Transition from Myocarditis to Dilated Cardiomyopathy and Heart Failure.International journal of molecular sciences · 2023Review
- Review
- Cytotoxic CD8Cells · 2022Article
- Advocacy of targeting protease-activated receptors in severe coronavirus disease 2019.British journal of pharmacology · 2022Article
- Inhibition of Protease Activated Receptor 2 Attenuates HBx-Induced Inflammation and Mitochondria Oxidative Stress.Infection and drug resistance · 2022Article
- Article
- Hypoxia-inducible transcription factor-1α inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes.Biomedical engineering online · 2021Article
- Cell type-specific roles of PAR1 in Coxsackievirus B3 infection.Scientific reports · 2021Article
- Review
- PAR1 regulation of CXCL1 expression and neutrophil recruitment to the lung in mice infected with influenza A virus.Journal of thrombosis and haemostasis : JTH · 2021Article
- Myeloid Protease-Activated Receptor-2 Contributes to Influenza A Virus Pathology in Mice.Frontiers in immunology · 2021Article
- PAR2 Promoter Hypomethylation Regulates PAR2 Gene Expression and Promotes Lung Adenocarcinoma Cell Progression.Computational and mathematical methods in medicine · 2021Article
- The pro-apoptosis and pro-inflammation role of LncRNA HIF1A-AS1 in Coxsackievirus B3-induced myocarditis via targeting miR-138.Cardiovascular diagnosis and therapy · 2020Article
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15 authors at 6 institutions in 2 countries.
Funding
Abstract
objectivesThis study sought to evaluate the role of protease-activated receptor-2 (PAR2) in coxsackievirus B3 (CVB3)-induced myocarditis.
backgroundAn infection with CVB3 leads to myocarditis. PAR2 modulates the innate immune response. Toll-like receptor-3 (TLR3) is crucial for the innate immune response by inducing the expression of the antiviral cytokine interferon-beta (IFNβ).
methodsTo induce myocarditis, wild-type (wt) and PAR2 knockout (ko) mice were infected with 10(5) plaque-forming units CVB3. Mice underwent hemodynamic measurements with a 1.2-F microconductance catheter. Wt and PAR2ko hearts and cardiac cells were analyzed for viral replication and immune response with plaque assay, quantitative polymerase chain reaction, Western blot, and immunohistochemistry.
resultsCompared with wt mice, PAR2ko mice and cardiomyocytes exhibited a reduced viral load and developed no myocarditis after infection with CVB3. Hearts and cardiac fibroblasts from PAR2ko mice expressed higher basal levels of IFNβ than wt mice did. Treatment with CVB3 and polyinosinic:polycytidylic acid led to higher IFNβ expression in PAR2ko than in wt fibroblasts and reduced virus replication in PAR2ko fibroblasts was abrogated by neutralizing IFNβ antibody. Overexpression of PAR2 reduced the basal IFNβ expression. Moreover, a direct interaction between PAR2 and Toll-like receptor 3 was observed. PAR2 expression in endomyocardial biopsies of patients with nonischemic cardiomyopathy was positively correlated with myocardial inflammation and negatively with IFNβ expression and left ventricular ejection fraction.
conclusionsPAR2 negatively regulates the innate immune response to CVB3 infection and contributes to myocardial dysfunction. The antagonism of PAR2 is of therapeutic interest to strengthen the antiviral response after an infection with a cardiotropic virus.
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