
This AOP is licensed under a Creative Commons Attribution 4.0 International License.
Aop: 319
Title
Inhibition of Angiotensin-converting enzyme 2 leading to lung fibrosis
Short name
Graphical Representation
Contributors
- Young Jun Kim
- Penny Nymark
- Brigitte Landesmann
Status
Author status | OECD status | OECD project | SAAOP status |
---|---|---|---|
Open for comment. Do not cite |
This AOP was last modified on March 25, 2021 14:12
Revision dates for related pages
Page | Revision Date/Time |
---|---|
Increase plasma Ang II | March 10, 2020 01:01 |
Increased Angiotensin II | April 04, 2021 08:00 |
ACE2 inhibition | March 10, 2020 00:54 |
Accumulation, Collagen | November 10, 2019 05:25 |
Lung fibrosis | December 26, 2017 02:10 |
ACE2 inhibition leads to Increased AngII | March 17, 2020 06:17 |
Increased AngII leads to Increase plasma Ang II | March 17, 2020 06:17 |
Increase plasma Ang II leads to Accumulation, Collagen | May 15, 2020 17:59 |
Accumulation, Collagen leads to Lung fibrosis | May 15, 2020 18:00 |
PM 2.5 | March 02, 2020 05:42 |
Streptozocin | April 26, 2020 05:50 |
Losartan | April 26, 2020 05:51 |
DX600 | February 11, 2021 10:25 |
cationic polyamidoamine dendrimer (nanoparticle) | February 11, 2021 10:29 |
Abstract
Lung fibrosis has a distinct point in idiopathic pulmonary fibrosis from the renin-angiotensin pathway. this system is reported in many works of literature to share many immune/inflammatory responses to lung damage. Most importantly, the Inhibition of ACE2 was shown to enhance the level of Ang II peptides which is a ligand for type 1 angiotensin receptor (AT1R) and is considered one of the risk factors for lung fibrosis, vasoconstriction, endothelial dysfunction, and cell death. The renin-angiotensin system plays a critical role in the fibrogenesis and inflammation damage of many organs. Especially the inhibition of membrane ACE-2 has shown promising potential in the Molecular initiation event which leading to pulmonary fibrosis. This AOP describes the role of ACE-2 in fibrotic damage of the lung as an adverse outcome through the fibrogenic components, proinflammatory cytokines, and oxygen deficiency.
Background (optional)
ACE2 is an essential enzyme of blood pressure regulation in the renin-angiotensin system. Angiotensin-converting enzyme (ACE) synthesizes the dominant vasoconstriction, inflammatory and profibrotic angiotensin II (Ang II) through its carboxypeptidase function on the decapeptide angiotensin I. In the meantime, Angiotensin-converting enzyme 2 (ACE2) is an exopeptidase that catalyzes the conversion of angiotensin Il to the conversion of angiotensin 1-7 function as vasodilation, anti-inflammation and anti-fibrotic. This AOP describes the dysfunction of membrane ACE2, which results in a high level of angiotensin Ang II synthesized by ACE, which can further lead to pulmonary fibrosis by excessive collagen deposition and interact with TGF beta as the most potent profibrotic factor.
Summary of the AOP
Events:
Molecular Initiating Events (MIE)
Key Events (KE)
Adverse Outcomes (AO)
Sequence | Type | Event ID | Title | Short name |
---|
MIE | 1740 | ACE2 inhibition | ACE2 inhibition |
KE | 1752 | Increased Angiotensin II | Increased AngII | |
KE | 1743 | Increase plasma Ang II | Increase plasma Ang II | |
KE | 68 | Accumulation, Collagen | Accumulation, Collagen |
AO | 1276 | Lung fibrosis | Lung fibrosis |
Relationships Between Two Key Events (Including MIEs and AOs)
Title | Adjacency | Evidence | Quantitative Understanding |
---|
ACE2 inhibition leads to Increased AngII | adjacent | High | Moderate |
Increased AngII leads to Increase plasma Ang II | adjacent | High | Moderate |
Increase plasma Ang II leads to Accumulation, Collagen | adjacent | Moderate | Moderate |
Accumulation, Collagen leads to Lung fibrosis | adjacent | High | High |
Network View
Stressors
Name | Evidence Term |
---|---|
PM 2.5 | High |
Streptozocin | High |
Losartan | High |
DX600 | High |
cationic polyamidoamine dendrimer (nanoparticle) | High |
Life Stage Applicability
Life stage | Evidence |
---|---|
Not Otherwise Specified | Moderate |
Taxonomic Applicability
Term | Scientific Term | Evidence | Link |
---|---|---|---|
mouse | Mus musculus | High | NCBI |