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Cited by 74Viral Infections and Immunology ResearchInflammasome and immune disordersCardiac Fibrosis and Remodeling

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Colchicine Prevents Disease Progression in Viral Myocarditis Via Modulating the NLRP3 Inflammasome in the Cardiosplenic Axis

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Pappritz, Kathleen, Lin, Jie, El-Shafeey, Muhammad, Fechner, Henry, Kühl, Uwe, Alogna, Alessio, Spillmann, Frank, Elsanhoury, Ahmed, Schulz, Rainer, Tschöpe, Carsten, Van Linthout, Sophie·2022·ESC Heart Failure
DOI 10.1002/ehf2.13845PMC PMC8934990
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Abstract

Aim: The acute phase of a coxsackievirus 3 (CVB3)-induced myocarditis involves direct toxic cardiac effects and the systemic activation of the immune system, including the cardiosplenic axis. Consequently, the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing-3 (NLRP3) inflammasome pathway is activated, which plays a role in disease pathogenesis and progression. The anti-inflammatory drug colchicine exerts its effects, in part, via reducing NLRP3 activity, and has been shown to improve several cardiac diseases, including acute coronary syndrome and pericarditis. The aim of the present study was to evaluate the potential of colchicine to improve experimental CVB3-induced myocarditis. Methods and results: C57BL6/j mice were intraperitoneally injected with 1 × 105 plaque forming units of CVB3. After 24 h, mice were treated with colchicine (5 μmol/kg body weight) or phosphate-buffered saline (PBS) via oral gavage (p.o.). Seven days post infection, cardiac function was haemodynamically characterized via conductance catheter measurements. Blood, the left ventricle (LV) and spleen were harvested for subsequent analyses. In vitro experiments on LV-derived fibroblasts (FB) and HL-1 cells were performed to further evaluate the anti-(fibro)inflammatory and anti-apoptotic effects of colchicine via gene expression analysis, Sirius Red assay, and flow cytometry. CVB3 + colchicine mice displayed improved LV function compared with CVB3 + PBS mice, paralleled by a 4.7-fold (P < 0.01) and 1.7-fold (P < 0.001) reduction in LV CVB3 gene expression and cardiac troponin-I levels in the serum, respectively. Evaluation of components of the NLRP3 inflammasome revealed an increased percentage of apoptosis-associated speck-like protein containing a CARD domain (ASC)-expressing, caspase-1-expressing, and interleukin-1β-expressing cells in the myocardium and in the spleen of CVB3 + PBS vs. control mice, which was reduced in CVB3 + colchicine compared with CVB3 + PBS mice. This was accompanied by 1.4-fold (P < 0.0001), 1.7-fold (P < 0.0001), and 1.7-fold (P < 0.0001) lower numbers of cardiac dendritic cells, natural killer cells, and macrophages, respectively, in CVB3 + colchicine compared with CVB3 + PBS mice. A 1.9-fold (P < 0.05) and 4.6-fold (P < 0.001) reduced cardiac gene expression of the fibrotic markers, Col1a1 and lysyl oxidase, respectively, was detected in CVB3 + colchicine mice compared with CVB3 + PBS animals, and reflected by a 2.2-fold (P < 0.05) decreased Collagen I/III protein ratio. Colchicine further reduced Col3a1 mRNA and collagen protein expression in CVB3-infected FB and lowered apoptosis and viral progeny release in CVB3-infected HL-1 cells. In both CVB3 FB and HL-1 cells, colchicine down-regulated the NLRP3 inflammasome-related components ASC, caspase-1, and IL-1β. Conclusions: Colchicine improves LV function in CVB3-induced myocarditis, involving a decrease in cardiac and splenic NLRP3 inflammasome activity, without exacerbation of CVB3 load.

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  • Inhibition of TLR4 and NLRP3 pathways reduces myocarditis in mouse models.

    “Importantly, inhibition of TLR4 and NLRP3 pathways reduces myocarditis in mouse models. 161,168”

    From COVID-19, Myocarditis and Pericarditis (2023) · cites this paper as [168]

    The Results (page not provided) report reduced cardiac NLRP3-inflammasome markers in colchicine-treated mice with CVB3-induced myocarditis, and the Discussion links treatment to reduced cardiac inflammation. The paper does not establish that inhibiting TLR4 reduces myocarditis; its NLRP3 finding therefore supports only part of the cited sentence. (LLM, conf=0.88)

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Research works printed but not linked: 46

  1. Tschope, 2019, Management of myocarditis-related cardiomyopathy in adults, Circ Res, 124, 1568, 10.1161/CIRCRESAHA.118.313578 · DOI
  2. Van Linthout, 2020, SARS-CoV-2-related myocarditis-like syndromes Shakespeare's question: what's in a name?, Eur J Heart Fail, 22, 922, 10.1002/ejhf.1899 · DOI
  3. Tschope, 2021, Myocarditis and inflammatory cardiomyopathy: current evidence and future directions, Nat Rev Cardiol, 18, 169, 10.1038/s41569-020-00435-x · DOI · Paper page
  4. Klingel, 1996, Pathogenesis of murine enterovirus myocarditis: virus dissemination and immune cell targets, J Virol, 70, 8888, 10.1128/jvi.70.12.8888-8895.1996 · DOI
  5. Leuschner, 2015, Silencing of CCR2 in myocarditis, Eur Heart J, 36, 1478, 10.1093/eurheartj/ehu225 · DOI
  6. Latz, 2013, Activation and regulation of the inflammasomes, Nat Rev Immunol, 13, 397, 10.1038/nri3452 · DOI · Paper page
  7. Toldo, 2014, Formation of the inflammasome in acute myocarditis, Int J Cardiol, 171, e119, 10.1016/j.ijcard.2013.12.137 · DOI
  8. Miteva, 2018, Mesenchymal stromal cells inhibit NLRP3 inflammasome activation in a model of coxsackievirus B3-induced inflammatory cardiomyopathy, Sci Rep, 8, 2820, 10.1038/s41598-018-20686-6 · DOI
  9. Tschöpe, 2017, NOD2 (nucleotide-binding oligomerization domain 2) is a major pathogenic mediator of coxsackievirus B3-induced myocarditis, Circ Heart Fail, 10, 10.1161/CIRCHEARTFAILURE.117.003870 · DOI · Paper page
  10. Nuki, 2008, Colchicine: its mechanism of action and efficacy in crystal-induced inflammation, Curr Rheumatol Rep, 10, 218, 10.1007/s11926-008-0036-3 · DOI
  11. Chaldakov, 2018, Colchicine, a microtubule-disassembling drug, in the therapy of cardiovascular diseases, Cell Biol Int, 42, 1079, 10.1002/cbin.10988 · DOI
  12. Akodad, 2017, Interest of colchicine in the treatment of acute myocardial infarct responsible for heart failure in a mouse model, Int J Cardiol, 240, 347, 10.1016/j.ijcard.2017.03.126 · DOI
  13. Cosyns, 2015, European Association of Cardiovascular Imaging (EACVI) position paper: multimodality imaging in pericardial disease, Eur Heart J Cardiovasc Imaging, 16, 12, 10.1093/ehjci/jeu128 · DOI
  14. Adler, 2015, 2015 ESC guidelines for the diagnosis and management of pericardial diseases: the task force for the diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC) endorsed by: the European Association for Cardio-Thoracic Surgery (EACTS), Eur Heart J, 36, 2921, 10.1093/eurheartj/ehv318 · DOI
  15. Pappritz, 2018, Immunomodulation by adoptive regulatory T-cell transfer improves coxsackievirus B3-induced myocarditis, FASEB J, 10.1096/fj.201701408R · DOI
  16. Pappritz, 2018, Cardiac (myo)fibroblasts modulate the migration of monocyte subsets, Sci Rep, 8, 10.1038/s41598-018-23881-7 · DOI
  17. Van Linthout, 2011, Mesenchymal stem cells improve murine acute coxsackievirus B3-induced myocarditis, Eur Heart J, 32, 2168, 10.1093/eurheartj/ehq467 · DOI
  18. Miteva, 2011, Human cardiac-derived adherent proliferating cells reduce murine acute coxsackievirus B3-induced myocarditis, PLoS ONE, 6, 10.1371/journal.pone.0028513 · DOI
  19. Miteva, 2017, Mesenchymal stromal cells modulate monocytes trafficking in coxsackievirus B3-induced myocarditis, Stem Cells Transl Med, 6, 1249, 10.1002/sctm.16-0353 · DOI
  20. Spillmann, 2015, High-density lipoproteins reduce endothelial-to-mesenchymal transition, Arterioscler Thromb Vasc Biol, 35, 1774, 10.1161/ATVBAHA.115.305887 · DOI
  21. Van Linthout, 2018, Telbivudine in chronic lymphocytic myocarditis and human parvovirus B19 transcriptional activity, ESC Heart Fail, 5, 818, 10.1002/ehf2.12341 · DOI
  22. Spillmann, 2006, Regional and global protective effects of tissue kallikrein gene delivery to the peri-infarct myocardium, Regen Med, 1, 235, 10.2217/17460751.1.2.235 · DOI
  23. Van Linthout, 2008, Human apolipoprotein A-I gene transfer reduces the development of experimental diabetic cardiomyopathy, Circulation, 117, 1563, 10.1161/CIRCULATIONAHA.107.710830 · DOI
  24. Müller, 2017, CX3CR1 knockout aggravates coxsackievirus B3-induced myocarditis, PLoS ONE, 12, 10.1371/journal.pone.0182643 · DOI
  25. Müller, 2017, Pathogenic role of the damage-associated molecular patterns S100A8 and S100A9 in coxsackievirus B3-induced myocarditis, Circ Heart Fail, 10, 10.1161/CIRCHEARTFAILURE.117.004125 · DOI
  26. Ismahil, 2014, Remodeling of the mononuclear phagocyte network underlies chronic inflammation and disease progression in heart failure: critical importance of the cardiosplenic axis, Circ Res, 114, 266, 10.1161/CIRCRESAHA.113.301720 · DOI
  27. Zhang, 2021, Regulation and functions of NLRP3 inflammasome in cardiac fibrosis: current knowledge and clinical significance, Biomed Pharmacother, 143, 10.1016/j.biopha.2021.112219 · DOI
  28. Kühl, 2003, Interferon-beta treatment eliminates cardiotropic viruses and improves left ventricular function in patients with myocardial persistence of viral genomes and left ventricular dysfunction, Circulation, 107, 2793, 10.1161/01.CIR.0000072766.67150.51 · DOI
  29. Tschöpe, 2020, Modulation of the acute defence reaction by eplerenone prevents cardiac disease progression in viral myocarditis, ESC Heart Fail, 7, 2838, 10.1002/ehf2.12887 · DOI
  30. Van Linthout, 2019, The quest for antiinflammatory and immunomodulatory strategies in heart failure, Clin Pharmacol Ther, 106, 1198, 10.1002/cpt.1637 · DOI
  31. Elsanhoury, 2020, A toolbox of potential immune-related therapies for inflammatory cardiomyopathy, J Cardiovasc Transl Res, 14, 75, 10.1007/s12265-020-10025-4 · DOI
  32. Bao, 2019, Macrophage NLRP3 inflammasome activated by CVB3 capsid proteins contributes to the development of viral myocarditis, Mol Immunol, 114, 41, 10.1016/j.molimm.2019.07.012 · DOI
  33. Wang, 2014, Involvement of NLRP3 inflammasome in CVB3-induced viral myocarditis, Am J Physiol Heart Circ Physiol, 307, H1438, 10.1152/ajpheart.00441.2014 · DOI
  34. Wang, 2019, NLRP3 deficiency exacerbates enterovirus infection in mice, FASEB J, 33, 942, 10.1096/fj.201800301RRR · DOI
  35. Smilde, 2016, Colchicine aggravates coxsackievirus B3 infection in mice, Int J Cardiol, 216, 58, 10.1016/j.ijcard.2016.04.144 · DOI
  36. Maestroni, 2017, Is colchicine really harmful in viral myocarditis?, Int J Cardiol, 229, 42, 10.1016/j.ijcard.2016.10.031 · DOI
  37. Milner, 2006, TSG-6: a pluripotent inflammatory mediator?, Biochem Soc Trans, 34, 446, 10.1042/BST0340446 · DOI
  38. Craig, 2008, Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice, J Clin Invest, 118, 3170, 10.1172/JCI34279 · DOI
  39. Feng, 2000, Colchicine protects mice from the lethal effect of an agonistic anti-Fas antibody, J Clin Invest, 105, 329, 10.1172/JCI7398 · DOI
  40. Bracey, 2014, Mitochondrial NLRP3 protein induces reactive oxygen species to promote Smad protein signaling and fibrosis independent from the inflammasome, J Biol Chem, 289, 19571, 10.1074/jbc.M114.550624 · DOI
  41. Ershaid, 2019, NLRP3 inflammasome in fibroblasts links tissue damage with inflammation in breast cancer progression and metastasis, Nat Commun, 10, 10.1038/s41467-019-12370-8 · DOI
  42. Fujisue, 2017, Colchicine improves survival, left ventricular remodeling, and chronic cardiac function after acute myocardial infarction, Circ J, 81, 1174, 10.1253/circj.CJ-16-0949 · DOI
  43. Tavazzi, 2020, Myocardial localization of coronavirus in COVID-19 cardiogenic shock, Eur J Heart Fail, 22, 911, 10.1002/ejhf.1828 · DOI
  44. Shi, 2019, SARS-coronavirus open reading frame-8b triggers intracellular stress pathways and activates NLRP3 inflammasomes, Cell Death Dis, 5
  45. Siu, 2019, Severe acute respiratory syndrome coronavirus ORF3a protein activates the NLRP3 inflammasome by promoting TRAF3-dependent ubiquitination of ASC, FASEB J, 33, 8865, 10.1096/fj.201802418R · DOI
  46. Deftereos, 2020, Effect of colchicine vs standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019: the GRECCO-19 randomized clinical trial, JAMA Netw Open, 3, 10.1001/jamanetworkopen.2020.13136 · DOI

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Metadata

Authors
Pappritz, K., Lin, J., El-Shafeey, M., Fechner, H., Kühl, U., Alogna, A., Spillmann, F., Elsanhoury, A., Schulz, R., Tschöpe, C., & Van Linthout, S.
Affiliations
  • Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
  • Justus-Liebig-Universität Gießen (DE)
  • Technische Universität Berlin (DE)
  • Charité – Universitätsmedizin Berlin (DE)
  • BIH Center for Regenerative Therapies (BCRT), Berlin Institute of Health at Charité, Universitätmedizin Berlin , Berlin ,
ORCID
Venue
ESC Heart Failure
Publisher
Oxford University Press (OUP)
Published
2022-02-17
Volume
9
Issue
2
Pages
925-941
ISSN
2055-5822 (ISSN-L)
DOI
10.1002/ehf2.13845
PMC
PMC8934990
OpenAlex
W4213186208
Cited by
74
References
2
Citations by year
2026: 12 · 2025: 18 · 2024: 17 · 2023: 20 · 2022: 7
FWCI
11.13
Type
journal article
Language
en
Open access
Licence
Locations
  • ESC Heart Failure (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Refubium (Universitätsbibliothek der Freien Universität Berlin) (submittedVersion, cc-by-nc-nd)
  • Universitätsbibliothek der FU Berlin Hochschulschriftenstelle u. Dokumentenserver
Funders
Friede Springer Heart Foundation
Topics
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
colchicine, viral myocarditis, coxsackievirus B3, NLRP3 inflammasome, spleen, caspase-1, IL-1β, ASC, myocardial fibrosis, apoptosis, cardiac function, anti-inflammatory therapy, disease progression prevention, cardiomyocyte injury, fibroblasts, HL-1 cells
MeSH terms
NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Colchicine, Humans, Myocarditis, Disease Progression, Mice, Inflammasomes

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