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Aop: 319

AOP Title

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ACE2 inhibition leading to lung fibrosis

Short name:

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ACE2 inhibition, lung fibrosis

Graphical Representation

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Click to download graphical representation template

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Authors

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Point of Contact

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Young Jun Kim   (email point of contact)

Contributors

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  • Young Jun Kim
  • Penny Nymark
  • Brigitte Landesmann

Status

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Author status OECD status OECD project SAAOP status
Open for comment. Do not cite


This AOP was last modified on June 25, 2020 07:51

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Revision dates for related pages

Page Revision Date/Time
Increase plasma Ang II March 10, 2020 01:01
Increases AngII March 17, 2020 06:15
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 Increases AngII March 17, 2020 06:17
Increases 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

Abstract

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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. The inhibition of 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)

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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 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

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
MIE 1740 ACE2 inhibition ACE2 inhibition
KE 1752 Increases AngII Increases 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)

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Title Adjacency Evidence Quantitative Understanding
ACE2 inhibition leads to Increases AngII adjacent High Moderate
Increases 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

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Stressors

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Name Evidence Term
PM 2.5 High
Streptozocin High
Losartan High

Life Stage Applicability

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Life stage Evidence
Not Otherwise Specified Moderate

Taxonomic Applicability

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Term Scientific Term Evidence Link
mouse Mus musculus High NCBI

Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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