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 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 [Garvin et al.](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410499/).Quality Tags
Ontology Terms
Pathway Ontology : disease pathway cancer pathway
Disease : cancer
Bibliography
View all... |
- Bassett MH, White PC, Rainey WE; ''The regulation of aldosterone synthase expression.''; Mol Cell Endocrinol, 2004 PubMed Europe PMC Scholia
- Schwartz GL, Turner ST; ''Pharmacogenetics of antihypertensive drug responses.''; Am J Pharmacogenomics, 2004 PubMed Europe PMC Scholia
- 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
- Surks HK; ''cGMP-dependent protein kinase I and smooth muscle relaxation: a tale of two isoforms.''; Circ Res, 2007 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
- 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
- Weir MR; ''Effects of renin-angiotensin system inhibition on end-organ protection: can we do better?''; Clin Ther, 2007 PubMed Europe PMC Scholia
- Denninger JW, Marletta MA; ''Guanylate cyclase and the .NO/cGMP signaling pathway.''; Biochim Biophys Acta, 1999 PubMed Europe PMC Scholia
- 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
View all... |
External references
DataNodes
View all... |
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) ![]() | |
AGTR1 | GeneProduct | 185 (Entrez Gene) ![]() | |
AGTR2 | GeneProduct | 186 (Entrez Gene) ![]() | |
Aldosterone | Metabolite | 52-39-1 (CAS) ![]() | |
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) ![]() | |
Degradation | Pathway | ||
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) ![]() | |
Relaxation | Pathway | ||
SERPINE1 | GeneProduct | 5054 (Entrez Gene) ![]() | SERPINE1 codes for plasminogen activator inhibitor-1 (PAI-1) |
SERPING1 | GeneProduct | ENSG00000149131 (Ensembl) ![]() | |
TNF | GeneProduct | ENSG00000232810 (Ensembl) ![]() | |
VDR | GeneProduct | ENSG00000111424 (Ensembl) ![]() | |
Vitamin D3 | Metabolite | CHEBI:28940 (ChEBI) ![]() | |
bradykinin, des-arg(9) | Metabolite | CHEBI:133068 (ChEBI) ![]() | |
nitric oxide | Metabolite | CHEBI:16480 (ChEBI) ![]() |
Annotated Interactions
No annotated interactions