دورية أكاديمية
أعرض في EDS

Preferential uptake of SARS-CoV-2 by pericytes potentiates vascular damage and permeability in an organoid model of the microvasculature.

التفاصيل البيبلوغرافية
العنوان: Preferential uptake of SARS-CoV-2 by pericytes potentiates vascular damage and permeability in an organoid model of the microvasculature.
المؤلفون: Khan AO; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK., Reyat JS; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK., Hill H; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Bourne JH; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK., Colicchia M; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK., Newby ML; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK., Allen JD; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK., Crispin M; School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK., Youd E; Forensic Medicine and Science, University of Glasgow, Glasgow G12 8QQ, UK., Murray PG; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.; Health Research Institute, University of Limerick, Limerick V94 T9PX, Ireland., Taylor G; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Stamataki Z; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Richter AG; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Cunningham AF; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Pugh M; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Rayes J; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Vincent Drive, Birmingham B15 2TT, UK.
المصدر: Cardiovascular research [Cardiovasc Res] 2022 Dec 09; Vol. 118 (15), pp. 3085-3096.
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: SARS-CoV-2* , COVID-19*, Humans ; Antigens, Viral
مستخلص: Aims: Thrombotic complications and vasculopathy have been extensively associated with severe COVID-19 infection; however, the mechanisms inducing endotheliitis and the disruption of endothelial integrity in the microcirculation are poorly understood. We hypothesized that within the vessel wall, pericytes preferentially take up viral particles and mediate the subsequent loss of vascular integrity.
Methods and Results: Immunofluorescence of post-mortem patient sections was used to assess pathophysiological aspects of COVID-19 infection. The effects of COVID-19 on the microvasculature were assessed using a vascular organoid model exposed to live viral particles or recombinant viral antigens. We find increased expression of the viral entry receptor angiotensin-converting enzyme 2 on pericytes when compared to vascular endothelium and a reduction in the expression of the junctional protein CD144, as well as increased cell death, upon treatment with both live virus and/or viral antigens. We observe a dysregulation of genes implicated in vascular permeability, including Notch receptor 3, angiopoietin-2, and TEK. Activation of vascular organoids with interleukin-1β did not have an additive effect on vascular permeability. Spike antigen was detected in some patients' lung pericytes, which was associated with a decrease in CD144 expression and increased platelet recruitment and von Willebrand factor (VWF) deposition in the capillaries of these patients, with thrombi in large vessels rich in VWF and fibrin.
Conclusion: Together, our data indicate that direct viral exposure to the microvasculature modelled by organoid infection and viral antigen treatment results in pericyte infection, detachment, damage, and cell death, disrupting pericyte-endothelial cell crosstalk and increasing microvascular endothelial permeability, which can promote thrombotic and bleeding complications in the microcirculation.
Competing Interests: Conflict of interest: none declared.
(© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved.)
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معلومات مُعتمدة: FS/IBSRF/20/25039 United Kingdom BHF_ British Heart Foundation; MRF_MRF-169-0001-F-STAM-C0826 United Kingdom MRF MRF; MR/T001755/1 United Kingdom MRC_ Medical Research Council; INV-008813 United States GATES Bill & Melinda Gates Foundation; MR/N023706/1 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust; 218649/Z/19/Z United Kingdom WT_ Wellcome Trust; INV-008352 United States GATES Bill & Melinda Gates Foundation; AA/18/2/34218 United Kingdom BHF_ British Heart Foundation
فهرسة مساهمة: Keywords: COVID-19; Endothelial permeability; Organoids; SARS-CoV-2; Thrombosis; Vasculopathy
المشرفين على المادة: 0 (Antigens, Viral)
تواريخ الأحداث: Date Created: 20220616 Date Completed: 20221215 Latest Revision: 20240410
رمز التحديث: 20240410
مُعرف محوري في PubMed: PMC9214165
DOI: 10.1093/cvr/cvac097
PMID: 35709328
قاعدة البيانات: MEDLINE
الوصف
تدمد:1755-3245
DOI:10.1093/cvr/cvac097