ROS in COVID-19 endothelial dysfunction (Homo sapiens)

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8511412641117369810119SARS-CoV-2NucleusEndothelial cellIncreased permeabilityDisturbed vascular tone ACE2NFKB1TNFRSF1AIFNAR1IFNA1Nitric oxideReactive oxygen speciesAngiotensin IIACE2TNFNOX1ICAM1RAS signalingACE2 (truncated)2ICAM1ACE2 (truncated)IFN signaling


Description

Proposed mechanism for COVID-19 induced endothelial dysfunction via ROS, as described by Ma et Al. (2022).

TNF-α stimulation of NADPH oxidase leads to accumulation of reactive oxygen species (ROS). Increased levels of IFN reduces the expression of functional ACE2, which leads to increased ROS via imbalanced RAS signaling. Excessive ROS disturbs vascular tone and increases endothelial permeability.

Description modified from Ma et. al..

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Bibliography

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  1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B; ''Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.''; Lancet, 2020 PubMed Europe PMC Scholia
  2. Zhong J, Guo D, Chen CB, Wang W, Schuster M, Loibner H, Penninger JM, Scholey JW, Kassiri Z, Oudit GY; ''Prevention of angiotensin II-mediated renal oxidative stress, inflammation, and fibrosis by angiotensin-converting enzyme 2.''; Hypertension, 2011 PubMed Europe PMC Scholia
  3. ''ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis''; J Leukoc Biol., 2020
  4. Verdecchia P, Cavallini C, Spanevello A, Angeli F; ''''; , PubMed Europe PMC Scholia
  5. Ma Z, Yang KY, Huang Y, Lui KO; ''Endothelial contribution to COVID-19: an update on mechanisms and therapeutic implications.''; J Mol Cell Cardiol, 2022 PubMed Europe PMC Scholia
  6. Ng KW, Attig J, Bolland W, Young GR, Major J, Wrobel AG, Gamblin S, Wack A, Kassiotis G; ''Tissue-specific and interferon-inducible expression of nonfunctional ACE2 through endogenous retroelement co-option.''; Nat Genet, 2020 PubMed Europe PMC Scholia
  7. ''NADPH oxidases, reactive oxygen species, and the kidney: friend and foe''; J Am Soc Nephrol., 2013 PubMed Europe PMC Scholia
  8. Lin CC, Yang CC, Wang CY, Tseng HC, Pan CS, Hsiao LD, Yang CM; ''NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-α-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion.''; Front Pharmacol, 2015 PubMed Europe PMC Scholia
  9. Incalza MA, D'Oria R, Natalicchio A, Perrini S, Laviola L, Giorgino F; ''Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases.''; Vascul Pharmacol, 2018 PubMed Europe PMC Scholia
  10. Ding J, Yu M, Jiang J, Luo Y, Zhang Q, Wang S, Yang F, Wang A, Wang L, Zhuang M, Wu S, Xia Y, Lu D; ''Angiotensin II Decreases Endothelial Nitric Oxide Synthase PhosphorylationviaAT1R Nox/ROS/PP2A Pathway.''; Front Physiol, 2020 PubMed Europe PMC Scholia
  11. Roebuck KA; ''Oxidant stress regulation of IL-8 and ICAM-1gene expression: differential activation and binding of the transcription factors AP-1 and NF-kappaB (Review).''; Int J Mol Med, 1999 PubMed Europe PMC Scholia
  12. Park A, Iwasaki A; ''Type I and Type III Interferons - Induction, Signaling, Evasion, and Application to Combat COVID-19.''; Cell Host Microbe, 2020 PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
134248view00:19, 18 July 2024EweitzMitigate graphical discrepancy between PathVisio and Kaavio / Pvjs
134247view00:16, 18 July 2024EweitzMitigate poor layout for standard off-center labels
134246view00:13, 18 July 2024EweitzPad virus node, standardize case and node height, economize layout
134115view18:29, 21 June 2024EgonwAdded some missing publication info
132626view17:33, 7 June 2024Khanspersupdated mim-conversion interactions to plain arrow
129511view12:05, 3 May 2024Ash iyeralignment of 'increased permeability' updated.
129476view03:25, 24 April 2024EweitzModified title
129370view09:43, 27 March 2024MkutmonOntology Term : 'infectious disease pathway' added !
129369view09:43, 27 March 2024MkutmonOntology Term : 'disease pathway' added !
128499view04:07, 9 February 2024Khanspersspecified truncated ACE2
128498view04:04, 9 February 2024KhanspersModified description
128497view03:58, 9 February 2024Khanspersadded xref for ROS
128496view03:54, 9 February 2024KhanspersOntology Term : 'endothelial cell' added !
128495view03:53, 9 February 2024Khanspersconnected interaction
128494view03:52, 9 February 2024Khanspersupdated AngII, interactions representing transcription, added cell/nucleus label
123975view10:32, 9 September 2022EweitzModified title
123426view06:24, 26 July 2022EgonwOntology Term : 'COVID-19' added !
123223view14:24, 5 July 2022EAD2022New pathway

External references

DataNodes

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NameTypeDatabase referenceComment
ACE2 (truncated)GeneProductENSG00000130234 (Ensembl)
ACE2GeneProductENSG00000130234 (Ensembl)
Angiotensin IIMetaboliteHMDB01035 (HMDB)
ICAM1GeneProductENSG00000090339 (Ensembl)
IFN signalingPathway
IFNA1GeneProductENSG00000197919 (Ensembl)
IFNAR1GeneProductENSG00000142166 (Ensembl)
NFKB1GeneProductENSG00000109320 (Ensembl)
NOX1GeneProductNOX1 (HGNC)
Nitric oxideMetaboliteCHEBI:16480 (ChEBI)
RAS signalingPathway
Reactive oxygen speciesMetaboliteCHEBI:26523 (ChEBI)
TNFGeneProductENSG00000232810 (Ensembl)
TNFRSF1AGeneProductENSG00000067182 (Ensembl)

Annotated Interactions

No annotated interactions

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