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Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19

The rapid ability of SARS-CoV-2 to spread among humans, along with the clinical complications of coronavirus disease 2019—COVID-19, have represented a significant challenge to the health management systems worldwide. The acute inflammation and coagulation abnormalities appear as the main causes for...

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Main Authors:	Argañaraz, Gustavo Adolfo, Palmeira, Julys da Fonseca, Argañaraz, Enrique Roberto
Format:	Artigo
Language:	Inglês
Published:	BMC 2021
Subjects:	Covid-19 - fisiopatologia Coagulação intravascular disseminada ADAM17 Fosfatidilserina
Online Access:	https://repositorio.unb.br/handle/10482/39923 https://doi.org/10.1186/s12964-020-00687-7 https://orcid.org/0000-0002-1612-2411 https://orcid.org/0000-0002-2724-369X https://orcid.org/0000-0002-4359-7594
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spelling	ir-10482-399232021-01-18T12:56:00Z Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19 Argañaraz, Gustavo Adolfo Palmeira, Julys da Fonseca Argañaraz, Enrique Roberto Covid-19 - fisiopatologia Coagulação intravascular disseminada ADAM17 Fosfatidilserina The rapid ability of SARS-CoV-2 to spread among humans, along with the clinical complications of coronavirus disease 2019—COVID-19, have represented a significant challenge to the health management systems worldwide. The acute inflammation and coagulation abnormalities appear as the main causes for thousands of deaths worldwide. The intense inflammatory response could be involved with the formation of thrombi. For instance, the presence of uncleaved large multimers of von Willebrand (vWF), due to low ADAMTS13 activity in plasma could be explained by the inhibitory action of pro-inflammatory molecules such as IL-1β and C reactive protein. In addition, the damage to endothelial cells after viral infection and/or activation of endothelium by pro-inflammatory cytokines, such as IL-1β, IL-6, IFN-γ, IL-8, and TNF-α induces platelets and monocyte aggregation in the vascular wall and expression of tissue factor (TF). The TF expression may culminate in the formation of thrombi, and activation of cascade by the extrinsic pathway by association with factor VII. In this scenario, the phosphatidylserine—PtdSer exposure on the outer leaflet of the cell membrane as consequence of viral infection emerges as another possible underlying mechanism to acute immune inflammatory response and activation of coagulation cascade. The PtdSer exposure may be an important mechanism related to ADAM17—mediated ACE2, TNF-α, EGFR and IL-6R shedding, and the activation of TF on the surface of infected endothelial cells. In this review, we address the underlying mechanisms involved in the pathophysiology of inflammation and coagulation abnormalities. Moreover, we introduce key biochemical and pathophysiological concepts that support the possible participation of PtdSer exposure on the outer side of the SARS-CoV-2 infected cells membrane, in the pathophysiology of COVID-19. 2021-01-18T12:56:00Z 2021-01-18T12:56:00Z 2020-12-27 Artigo ARGAÑARAZ, Gustavo A.; PALMEIRA, Julys da Fonseca; ARGAÑARAZ, Enrique R. Phosphatidylserine inside out: a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19. Cell Communication and Signaling, v. 18, art. n. 190, 2020. DOI: https://doi.org/10.1186/s12964-020-00687-7. Disponível em: https://biosignaling.biomedcentral.com/articles/10.1186/s12964-020-00687-7. Acesso em: 18 jan. 2021. https://repositorio.unb.br/handle/10482/39923 https://doi.org/10.1186/s12964-020-00687-7 https://orcid.org/0000-0002-1612-2411 https://orcid.org/0000-0002-2724-369X https://orcid.org/0000-0002-4359-7594 Inglês Acesso Aberto © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. application/pdf BMC
institution	REPOSITORIO UNB
collection	REPOSITORIO UNB
language	Inglês
topic	Covid-19 - fisiopatologia Coagulação intravascular disseminada ADAM17 Fosfatidilserina
spellingShingle	Covid-19 - fisiopatologia Coagulação intravascular disseminada ADAM17 Fosfatidilserina Argañaraz, Gustavo Adolfo Palmeira, Julys da Fonseca Argañaraz, Enrique Roberto Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19
description	The rapid ability of SARS-CoV-2 to spread among humans, along with the clinical complications of coronavirus disease 2019—COVID-19, have represented a significant challenge to the health management systems worldwide. The acute inflammation and coagulation abnormalities appear as the main causes for thousands of deaths worldwide. The intense inflammatory response could be involved with the formation of thrombi. For instance, the presence of uncleaved large multimers of von Willebrand (vWF), due to low ADAMTS13 activity in plasma could be explained by the inhibitory action of pro-inflammatory molecules such as IL-1β and C reactive protein. In addition, the damage to endothelial cells after viral infection and/or activation of endothelium by pro-inflammatory cytokines, such as IL-1β, IL-6, IFN-γ, IL-8, and TNF-α induces platelets and monocyte aggregation in the vascular wall and expression of tissue factor (TF). The TF expression may culminate in the formation of thrombi, and activation of cascade by the extrinsic pathway by association with factor VII. In this scenario, the phosphatidylserine—PtdSer exposure on the outer leaflet of the cell membrane as consequence of viral infection emerges as another possible underlying mechanism to acute immune inflammatory response and activation of coagulation cascade. The PtdSer exposure may be an important mechanism related to ADAM17—mediated ACE2, TNF-α, EGFR and IL-6R shedding, and the activation of TF on the surface of infected endothelial cells. In this review, we address the underlying mechanisms involved in the pathophysiology of inflammation and coagulation abnormalities. Moreover, we introduce key biochemical and pathophysiological concepts that support the possible participation of PtdSer exposure on the outer side of the SARS-CoV-2 infected cells membrane, in the pathophysiology of COVID-19.
format	Artigo
author	Argañaraz, Gustavo Adolfo Palmeira, Julys da Fonseca Argañaraz, Enrique Roberto
author_sort	Argañaraz, Gustavo Adolfo
title	Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19
title_short	Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19
title_full	Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19
title_fullStr	Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19
title_full_unstemmed	Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19
title_sort	phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of covid-19
publisher	BMC
publishDate	2021
url	https://repositorio.unb.br/handle/10482/39923 https://doi.org/10.1186/s12964-020-00687-7 https://orcid.org/0000-0002-1612-2411 https://orcid.org/0000-0002-2724-369X https://orcid.org/0000-0002-4359-7594
_version_	1690679527199473664
score	13.657419

Phosphatidylserine inside out : a possible underlying mechanism in the infammation and coagulation abnormalities of COVID-19

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