RAS and bradykinin pathways in COVID-19 (Homo sapiens)
From WikiPathways
Description
This pathway describes imbalances in RAS and Bradykinin pathways in COVID-19.
The expression of several genes in this pathway 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 Garvin et al.Quality Tags
Ontology Terms
Bibliography
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- Vianna RM, Calixto JB; ''Characterization of the receptor and the mechanisms underlying the inflammatory response induced by des-Arg9-BK in mouse pleurisy.''; Br J Pharmacol, 1998 PubMed Europe PMC Scholia
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- de Maat S, de Mast Q, Danser AHJ, van de Veerdonk FL, Maas C; ''Impaired Breakdown of Bradykinin and Its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection.''; Semin Thromb Hemost, 2020 PubMed Europe PMC Scholia
- Carvalho PR, Sirois P, Fernandes PD; ''The role of kallikrein-kinin and renin-angiotensin systems in COVID-19 infection.''; Peptides, 2020 PubMed Europe PMC Scholia
- Batenburg WW, Jan Danser AH; ''The (pro)renin receptor: a new addition to the renin-angiotensin system?''; Eur J Pharmacol, 2008 PubMed Europe PMC Scholia
- Huang Y, Wongamorntham S, Kasting J, McQuillan D, Owens RT, Yu L, Noble NA, Border W; ''Renin increases mesangial cell transforming growth factor-beta1 and matrix proteins through receptor-mediated, angiotensin II-independent mechanisms.''; Kidney Int, 2006 PubMed Europe PMC Scholia
- D'Alonzo D, De Fenza M, Pavone V; ''COVID-19 and pneumonia: a role for the uPA/uPAR system.''; Drug Discov Today, 2020 PubMed Europe PMC Scholia
- Ferreira AJ, Raizada MK; ''Are we poised to target ACE2 for the next generation of antihypertensives?''; J Mol Med, 2008 PubMed Europe PMC Scholia
- ''Endothelium Infection and Dysregulation by SARS-CoV-2: Evidence and Caveats in COVID-19''; Viruses, 2020 PubMed Europe PMC Scholia
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- Maron BA, Leopold JA; ''Mineralocorticoid receptor antagonists and endothelial function.''; Curr Opin Investig Drugs, 2008 PubMed Europe PMC Scholia
- de Maat S, de Mast Q, Danser AHJ, van de Veerdonk FL, Maas C; ''Impaired Breakdown of Bradykinin and Its Metabolites as a Possible Cause for Pulmonary Edema in COVID-19 Infection.''; Semin Thromb Hemost, 2020 PubMed Europe PMC Scholia
- Li P, Kondo T, Numaguchi Y, Kobayashi K, Aoki M, Inoue N, Okumura K, Murohara T; ''Role of bradykinin, nitric oxide, and angiotensin II type 2 receptor in imidapril-induced angiogenesis.''; Hypertension, 2008 PubMed Europe PMC Scholia
- Alessi D, MacDougall LK, Sola MM, Ikebe M, Cohen P; ''The control of protein phosphatase-1 by targetting subunits. The major myosin phosphatase in avian smooth muscle is a novel form of protein phosphatase-1.''; Eur J Biochem, 1992 PubMed Europe PMC Scholia
- Garvin MR, Alvarez C, Miller JI, Prates ET, Walker AM, Amos BK, Mast AE, Justice A, Aronow B, Jacobson D; ''A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm''; eLife, 2020
- Vianna RM, Calixto JB; ''Characterization of the receptor and the mechanisms underlying the inflammatory response induced by des-Arg9-BK in mouse pleurisy.''; Br J Pharmacol, 1998 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
20-HETE | Metabolite | CHEBI:34306 (ChEBI) | |
ACE | GeneProduct | 1636 (Entrez Gene) | |
ACE2 | GeneProduct | 59272 (Entrez Gene) | |
ACE2 | GeneProduct | ENSG00000130234 (Ensembl) | |
AGT | GeneProduct | 183 (Entrez Gene) | |
AGTR2 | GeneProduct | 186 (Entrez Gene) | |
Ang 1-7 | Metabolite | 110354 (Chemspider) | |
Ang 1-9 | Metabolite | C15851 (KEGG Compound) | |
Angiotensin I | Metabolite | 3081372 (PubChem-compound) | |
Angiotensin II | Metabolite | HMDB0001035 (HMDB) | |
Arachidonic acid | Metabolite | CHEBI:15843 (ChEBI) | |
BDKRB1 | GeneProduct | 623 (Entrez Gene) | |
BDKRB2 | GeneProduct | 624 (Entrez Gene) | |
Bradykinin | Metabolite | HMDB0004246 (HMDB) | |
CPN1 | GeneProduct | ENSG00000120054 (Ensembl) | |
CYP24A1 | GeneProduct | ENSG00000019186 (Ensembl) | |
CYP3A4 | GeneProduct | ENSG00000160868 (Ensembl) | |
Ca++ | Metabolite | HMDB0000464 (HMDB) | |
Complement and Coagulation Cascades | Pathway | WP558 (WikiPathways) | |
Cyclic guanosine monophosphate | Metabolite | CHEBI:16356 (ChEBI) | |
F12 | GeneProduct | ENSG00000131187 (Ensembl) | |
Guanosine triphosphate | Metabolite | CHEBI:15996 (ChEBI) | |
Guanylate cyclase | Protein | A0A140VJE6 (Uniprot-TrEMBL) | |
IL1A | GeneProduct | IL1A (HGNC) | |
IL1B | GeneProduct | IL1B (HGNC) | |
KLK1 | GeneProduct | ENSG00000167748 (Ensembl) | |
KLKB1 | GeneProduct | ENSG00000164344 (Ensembl) | |
KNG1 | GeneProduct | 3827 (Entrez Gene) | |
Kallikrein-Kinin System | Pathway | ||
L-arginine | Metabolite | CHEBI:16467 (ChEBI) | |
MAPK1 | GeneProduct | ENSG00000100030 (Ensembl) | |
MLCP | Complex | 3.1.3.53 (BRENDA) | |
NFKB1 | GeneProduct | ENSG00000109320 (Ensembl) | |
NFKB1 | GeneProduct | NFKB1 (HGNC) | |
NOS1 | GeneProduct | ENSG00000089250 (Ensembl) | |
NOS3 | GeneProduct | ENSG00000164867 (Ensembl) | |
PRKG1 | GeneProduct | ENSG00000185532 (Ensembl) | |
Prostaglandin E2 | Metabolite | 363-24-6 (CAS) | |
Prostaglandin I2 | Metabolite | 35121-78-9 (CAS) | |
REN | GeneProduct | 5972 (Entrez Gene) | |
RHOA | GeneProduct | ENSG00000067560 (Ensembl) | |
ROCK1 | GeneProduct | ENSG00000067900 (Ensembl) | |
SERPING1 | GeneProduct | ENSG00000149131 (Ensembl) | |
TNF | GeneProduct | ENSG00000232810 (Ensembl) | |
VDR | GeneProduct | ENSG00000111424 (Ensembl) | |
Vitamin D3 | Metabolite | CHEBI:28940 (ChEBI) | |
bradykinin, des-arg(9) | Metabolite | CHEBI:133069 (ChEBI) | |
nitric oxide | Metabolite | CHEBI:16480 (ChEBI) |
Annotated Interactions
No annotated interactions