SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung.
Anticoagulants
/ metabolism
Blood Coagulation
/ genetics
Bronchoalveolar Lavage Fluid
COVID-19
/ genetics
Endothelial Protein C Receptor
/ genetics
Fibrin
/ genetics
Gene Expression
Humans
Kallikrein-Kinin System
/ genetics
Kallikreins
/ genetics
Kinins
/ genetics
Lung
/ metabolism
RNA, Messenger
/ metabolism
SARS-CoV-2
Sequence Analysis, RNA
Thrombomodulin
/ genetics
Urokinase-Type Plasminogen Activator
/ genetics
COVID-19
SARS-CoV-2
bronchoalvelolar
coagulation
epidemiology
fibrinolysis
global health
human
medicine
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
08 03 2021
08 03 2021
Historique:
received:
26
10
2020
accepted:
06
03
2021
pubmed:
9
3
2021
medline:
22
4
2021
entrez:
8
3
2021
Statut:
epublish
Résumé
Extensive fibrin deposition in the lungs and altered levels of circulating blood coagulation proteins in COVID-19 patients imply local derangement of pathways that limit fibrin formation and/or promote its clearance. We examined transcriptional profiles of bronchoalveolar lavage fluid (BALF) samples to identify molecular mechanisms underlying these coagulopathies. mRNA levels for regulators of the kallikrein-kinin (C1-inhibitor), coagulation (thrombomodulin, endothelial protein C receptor), and fibrinolytic (urokinase and urokinase receptor) pathways were significantly reduced in COVID-19 patients. While transcripts for several coagulation proteins were increased, those encoding tissue factor, the protein that initiates coagulation and whose expression is frequently increased in inflammatory disorders, were not increased in BALF from COVID-19 patients. Our analysis implicates enhanced propagation of coagulation and decreased fibrinolysis as drivers of the coagulopathy in the lungs of COVID-19 patients.
Identifiants
pubmed: 33683204
doi: 10.7554/eLife.64330
pii: 64330
pmc: PMC8049742
doi:
pii:
Substances chimiques
Anticoagulants
0
Endothelial Protein C Receptor
0
Kinins
0
RNA, Messenger
0
Thrombomodulin
0
Fibrin
9001-31-4
Kallikreins
EC 3.4.21.-
Urokinase-Type Plasminogen Activator
EC 3.4.21.73
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIH HHS
ID : HL143403
Pays : United States
Organisme : NIH HHS
ID : HL068835
Pays : United States
Organisme : NHLBI NIH HHS
ID : U24 HL148865
Pays : United States
Organisme : NIA NIH HHS
ID : 3RF1AG053303-01S2
Pays : United States
Organisme : NIH HHS
ID : HL126974
Pays : United States
Organisme : NIH HHS
ID : U24 HL148865
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL140025
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : NIH HHS
ID : HL140025
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL126974
Pays : United States
Organisme : NIH HHS
ID : U24 HL148
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021, Mast et al.
Déclaration de conflit d'intérêts
AM receives research funding from Novo Nordisk and has received honoraria for serving on Novo Nordisk advisory boards. AW receives research funding from Takeda and Bristol Myers Squibb, DG receives research funding from Bayer and has received honoraria for serving on Anthos, Bristol-Myers Squibb, Ionis and Janssen advisory boards. MG, CA, JM, BA, DJ No competing interests declared
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