ACE2 inhibition leads to pulmonary fibrosis (WP5035)

Homo sapiens

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.

Authors

Marvin Martens , Finterly Hu , Alex Pico , and Eric Weitz

Activity

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Organisms

Homo sapiens

Communities

Adverse Outcome Pathways COVID-19

Annotations

Disease Ontology

pulmonary fibrosis COVID-19

Pathway Ontology

angiotensin II signaling pathway via AT1 receptor kallikrein-kinin cascade pathway

Cell Type Ontology

fibroblast

Participants

Label Type Compact URI Comment

References

  1. Understanding COVID-19 through adverse outcome pathways - 2nd CIAO AOP Design Workshop. Wittwehr C, Amorim MJ, Clerbaux LA, Krebs C, Landesmann B, Macmillan DS, et al. ALTEX. 2021;38(2):351–7. PubMed Europe PMC Scholia
  2. Systematic Organization of COVID-19 Data Supported by the Adverse Outcome Pathway Framework. Nymark P, Sachana M, Leite SB, Sund J, Krebs CE, Sullivan K, et al. Front Public Health. 2021 May 19;9:638605. PubMed Europe PMC Scholia
  3. COVID-19 through Adverse Outcome Pathways: Building networks to better understand the disease - 3rd CIAO AOP Design Workshop. Clerbaux LA, Amigó N, Amorim MJ, Bal-Price A, Batista Leite S, Beronius A, et al. ALTEX. 2022;39(2):322–35. PubMed Europe PMC Scholia