ACE2 inhibition leads to pulmonary fibrosis (Homo sapiens)
From WikiPathways
Description
This AOP outlines how ACE-2 plays a detrimental role in causing fibrotic damage to the lung by influencing various factors such as fibrogenic components, proinflammatory cytokines, and a lack of oxygen. When the activity of ACE2 is suppressed, the conversion of Ang II into Ang-(1-7) is not properly facilitated. Consequently, the levels of proinflammatory Ang II rise, while the levels of anti-inflammatory Ang-(1-7) decrease. Notably, ACE2 inhibition has been observed to raise the levels of Ang II peptides, which are a ligand for the type 1 angiotensin receptor (AT1R). This phenomenon is considered a significant risk factor for lung fibrosis, vasoconstriction, endothelial dysfunction, and cell death.
Quality Tags
Ontology Terms
Saving...Bibliography
- Clerbaux LA, Amigó N, Amorim MJ, Bal-Price A, Batista Leite S, Beronius A, Bezemer GFG, Bostroem AC, Carusi A, Coecke S, Concha R, Daskalopoulos EP, De Bernardi F, Edrosa E, Edwards SW, Filipovska J, Garcia-Reyero N, Gavins FNE, Halappanavar S, Hargreaves AJ, Hogberg HT, Huynh MT, Jacobson D, Josephs-Spaulding J, Kim YJ, Kong HJ, Krebs CE, Lam A, Landesmann B, Layton A, Lee YO, Macmillan DS, Mantovani A, Margiotta-Casaluci L, Martens M, Masereeuw R, Mayasich SA, Mei LM, Mortensen H, Munoz Pineiro A, Nymark P, Ohayon E, Ojasi J, Paini A, Parissis N, Parvatam S, Pistollato F, Sachana M, Sørli JB, Sullivan KM, Sund J, Tanabe S, Tsaioun K, Vinken M, Viviani L, Waspe J, Willett C, Wittwehr C; ''COVID-19 through Adverse Outcome Pathways: Building networks to better understand the disease - 3rd CIAO AOP Design Workshop.''; ALTEX, 2022 PubMed Europe PMC Scholia
- Wittwehr C, Amorim MJ, Clerbaux LA, Krebs C, Landesmann B, Macmillan DS, Nymark P, Ram R, Garcia-Reyero N, Sachana M, Sullivan K, Sund J, Willett C; ''Understanding COVID-19 through adverse outcome pathways - 2nd CIAO AOP Design Workshop.''; ALTEX, 2021 PubMed Europe PMC Scholia
- Nymark P, Sachana M, Leite SB, Sund J, Krebs CE, Sullivan K, Edwards S, Viviani L, Willett C, Landesmann B, Wittwehr C; ''Systematic Organization of COVID-19 Data Supported by the Adverse Outcome Pathway Framework.''; Front Public Health, 2021 PubMed Europe PMC Scholia
History
View all... |
External references
DataNodes
| View all... |
| Name | Type | Database reference | Comment |
|---|---|---|---|
| ACE2 inhibition | Pathway | WP554 (WikiPathways)  | |
| Angiotensin II receptor type 1 pathway | Pathway | WP5036 (WikiPathways) | |
| Binding of agonist, Angiotensin II receptor type 1 receptor (AT1R) | Event | 1851 (AOP-Wiki KE) | |
| Bradykinin signaling network | Pathway | WP5068 (WikiPathways) | |
| Bradykinin system, hyperactivated | 1867 (AOP-Wiki KE) | ||
| Collagen biosynthesis and modifying enzymes | Pathway | WP2725 (WikiPathways) | |
| Increase activation, Nuclear factor kappa B (NF-kB) | Event | 1172 (AOP-Wiki KE) | |
| Increased, Reactive oxygen species | Event | 1115 (AOP-Wiki KE) | |
| Increased, secretion of proinflammatory and profibrotic mediators | 1496 (AOP-Wiki KE) | ||
| KE1276: Lung Fibrosis | Event | 1276 (AOP-Wiki KE) | |
| KE1740: ACE2 inhibition | Event | 1740 (AOP-Wiki KE) | |
| KE1743: Increased plasma Angiotensin II | Event | 1743 (AOP-Wiki KE) | |
| KE1752: Increased Angiotensin II | Event | 1752 (AOP-Wiki KE) | |
| KE68: Collagen Accumulation | Event | 68 (AOP-Wiki KE) | |
| Kinin-Kallikrein Pathway | Pathway | WP5089 (WikiPathways) | |
| Metabolism of Angiotensinogen to Angiotensins | Pathway | WP2729 (WikiPathways) | |
| NF-KB pathway | Pathway | WP4562 (WikiPathways) | |
| Overview of proinflammatory and profibrotic mediators | Pathway | WP5095 (WikiPathways) | |
| Oxidative stress | Pathway | WP408 (WikiPathways) | |
| Prostaglandin signaling | Pathway | WP5088 (WikiPathways) | |
| Renin Angiotensin Aldosterone System | Pathway | WP4756 (WikiPathways) |
Annotated Interactions
No annotated interactions
