RAS and bradykinin pathways in COVID-19 (WP4969)

Homo sapiens

This pathway describes imbalances in RAS and Bradykinin pathways in COVID-19. The expression of several genes in these pathways is affected in by SARS-CoV-2: * SERPING1 is downregulated, which cancels the suppression of F12 of the intrinsic coagulation cascade, resulting in the production of bradykinin from kallikrein and KNG. * ACE is downregulated, which increases bradykinin levels. * ACE2 is upregulated, ACE is downregulated, which causes an increase in Angiotensin 1-9 and sensitization of bradykinin receptors. * NFkappaB is suppressed by SARS-Cov-2, decreasing its binding to the ACE promoter and subsequent transcription. The result of a hyperactive bradykinin system is vasodilation to the point of vascular leakage and infiltration of inflammatory cells. The pathway is based on figure 2A from [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410499/ Garvin et al.]


Kristina Hanspers , Egon Willighagen , Friederike Ehrhart , Marvin Martens , Penny Nymark , Eric Weitz , and Denise Slenter


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Homo sapiens




Pathway Ontology

disease pathway

Disease Ontology


Cell Type Ontology

vascular associated smooth muscle cell


Label Type Compact URI Comment
20-HETE Metabolite chebi:34306
Vitamin D3 Metabolite chebi:28940
bradykinin, des-arg(9) Metabolite chebi:133068
L-arginine Metabolite chebi:16467
Aldosterone Metabolite cas:52-39-1
Bradykinin Metabolite hmdb:HMDB0004246
Angiotensin II Metabolite hmdb:HMDB0001035
Angiotensin I Metabolite pubchem.compound:3081372
Ang 1-7 Metabolite chemspider:110354
Ang 1-9 Metabolite kegg.compound:C15851
Arachidonic acid Metabolite chebi:15843
Ca++ Metabolite hmdb:HMDB0000464
Guanosine triphosphate Metabolite chebi:15996
nitric oxide Metabolite chebi:16480
Cyclic guanosine monophosphate Metabolite chebi:16356
nitric oxide Metabolite chebi:16480
L-arginine Metabolite chebi:16467
Prostaglandin E2 Metabolite cas:363-24-6
Prostaglandin I2 Metabolite cas:35121-78-9
Prostaglandin E2 Metabolite cas:363-24-6
Prostaglandin I2 Metabolite cas:35121-78-9
SERPINE1 GeneProduct ncbigene:5054 SERPINE1 codes for plasminogen activator inhibitor-1 (PAI-1)
NFKB1 GeneProduct ensembl:ENSG00000109320
VDR GeneProduct ensembl:ENSG00000111424
MAPK1 GeneProduct ensembl:ENSG00000100030
SERPING1 GeneProduct ensembl:ENSG00000149131
CYP24A1 GeneProduct ensembl:ENSG00000019186
KLK1 GeneProduct ensembl:ENSG00000167748
F12 GeneProduct ensembl:ENSG00000131187
KLKB1 GeneProduct ensembl:ENSG00000164344
AGTR1 GeneProduct ncbigene:185
CPN1 GeneProduct ensembl:ENSG00000120054
AGTR2 GeneProduct ncbigene:186
BDKRB1 GeneProduct ncbigene:623
KNG1 GeneProduct ncbigene:3827
ACE GeneProduct ncbigene:1636
REN GeneProduct ncbigene:5972
ACE2 GeneProduct ncbigene:59272
AGT GeneProduct ncbigene:183
ACE GeneProduct ncbigene:1636
BDKRB2 GeneProduct ncbigene:624
CYP3A4 GeneProduct ensembl:ENSG00000160868
CYP3A4 GeneProduct ensembl:ENSG00000160868
ACE GeneProduct ncbigene:1636
PRKG1 GeneProduct ensembl:ENSG00000185532
RHOA GeneProduct ensembl:ENSG00000067560
ROCK1 GeneProduct ensembl:ENSG00000067900
NOS1 GeneProduct ensembl:ENSG00000089250
NOS3 GeneProduct ensembl:ENSG00000164867
ACE2 GeneProduct ensembl:ENSG00000130234
TNF GeneProduct ensembl:ENSG00000232810
IL1A GeneProduct hgnc.symbol:IL1A
NFKB1 GeneProduct hgnc.symbol:NFKB1
IL1B GeneProduct hgnc.symbol:IL1B
IL1A GeneProduct hgnc.symbol:IL1A
IL1B GeneProduct hgnc.symbol:IL1B
IL1A GeneProduct hgnc.symbol:IL1A
IL1B GeneProduct hgnc.symbol:IL1B
Guanylate cyclase Protein uniprot:A0A140VJE6


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