دورية أكاديمية
أعرض في EDS

Proinflammatory cytokines driving cardiotoxicity in COVID-19.

التفاصيل البيبلوغرافية
العنوان: Proinflammatory cytokines driving cardiotoxicity in COVID-19.
المؤلفون: Colzani M; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK.; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK., Bargehr J; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK.; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK., Mescia F; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK.; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, CB2 0AW Cambridge, UK., Williams EC; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK., Knight-Schrijver V; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK.; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK., Lee J; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK.; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK., Summers C; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK.; Wolfson Lung Injury Unit, Heart and Lung Research Institute, Cambridge Biomedical Campus, Papworth Road, CB2 0BB Cambridge, UK., Mohorianu I; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK., Smith KGC; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK.; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, CB2 0AW Cambridge, UK., Lyons PA; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK.; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Puddicombe Way, CB2 0AW Cambridge, UK., Sinha S; Wellcome - MRC Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge, Puddicombe Way, CB2 0AW Cambridge, UK.; Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Addenbrooke's Hospital, Hills Rd, CB2 0SP Cambridge, UK.
المصدر: Cardiovascular research [Cardiovasc Res] 2024 Mar 13; Vol. 120 (2), pp. 174-187.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford Journals Country of Publication: England NLM ID: 0077427 Publication Model: Print Cited Medium: Internet ISSN: 1755-3245 (Electronic) Linking ISSN: 00086363 NLM ISO Abbreviation: Cardiovasc Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 2008- : Oxford : Oxford Journals
Original Publication: London, British Medical Assn.
مواضيع طبية MeSH: COVID-19*, Humans ; Cytokines ; Cardiotoxicity ; Interleukin-6 ; Tumor Necrosis Factor-alpha
مستخلص: Aims: Cardiac involvement is common in patients hospitalized with COVID-19 and correlates with an adverse disease trajectory. While cardiac injury has been attributed to direct viral cytotoxicity, serum-induced cardiotoxicity secondary to serological hyperinflammation constitutes a potentially amenable mechanism that remains largely unexplored.
Methods and Results: To investigate serological drivers of cardiotoxicity in COVID-19 we have established a robust bioassay that assessed the effects of serum from COVID-19 confirmed patients on human embryonic stem cell (hESC)-derived cardiomyocytes. We demonstrate that serum from COVID-19 positive patients significantly reduced cardiomyocyte viability independent of viral transduction, an effect that was also seen in non-COVID-19 acute respiratory distress syndrome (ARDS). Serum from patients with greater disease severity led to worse cardiomyocyte viability and this significantly correlated with levels of key inflammatory cytokines, including IL-6, TNF-α, IL1-β, IL-10, CRP, and neutrophil to lymphocyte ratio with a specific reduction of CD4+ and CD8+ cells. Combinatorial blockade of IL-6 and TNF-α partly rescued the phenotype and preserved cardiomyocyte viability and function. Bulk RNA sequencing of serum-treated cardiomyocytes elucidated specific pathways involved in the COVID-19 response impacting cardiomyocyte viability, structure, and function. The observed effects of serum-induced cytotoxicity were cell-type selective as serum exposure did not adversely affect microvascular endothelial cell viability but resulted in endothelial activation and a procoagulant state.
Conclusion: These results provide direct evidence that inflammatory cytokines are at least in part responsible for the cardiovascular damage seen in COVID-19 and characterise the downstream activated pathways in human cardiomyocytes. The serum signature of patients with severe disease indicates possible targets for therapeutic intervention.
Competing Interests: Conflict of interest: None declared.
(© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
التعليقات: Comment in: Cardiovasc Res. 2024 Jan 25;:. (PMID: 38270957)
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معلومات مُعتمدة: United Kingdom WT_ Wellcome Trust; MC_PC_17230 United Kingdom MRC_ Medical Research Council; SP/15/7/31561 United Kingdom BHF_ British Heart Foundation; 077940/Z/05/Z United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Keywords: COVID-19; Cardiotoxicity; Inflammation; Stem cell derived cardiomyocytes
المشرفين على المادة: 0 (Cytokines)
0 (Interleukin-6)
0 (Tumor Necrosis Factor-alpha)
تواريخ الأحداث: Date Created: 20231202 Date Completed: 20240314 Latest Revision: 20240320
رمز التحديث: 20240320
مُعرف محوري في PubMed: PMC10936751
DOI: 10.1093/cvr/cvad174
PMID: 38041432
قاعدة البيانات: MEDLINE
الوصف
تدمد:1755-3245
DOI:10.1093/cvr/cvad174