The role of the classical renin-angiotensin system and angiotensin-converting enzyme 2/Ang(1-7)/Mas axis in pulmonary fibrosis.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and clinical pathways without systematic review methodology or primary data
PubMed 40800134 · doi:10.3389/fmed.2025.1615991
What was done
This narrative review synthesized current basic and clinical literature on the mechanistic involvement of the renin-angiotensin system (RAS)—specifically the classical Ang II/AT1R/AT2R pathways and the counter-regulatory ACE2/Ang(1-7)/Mas axis—in the pathogenesis and progression of pulmonary fibrosis.
What was found
The abstract provides no quantitative data. Mechanistically, it notes that Ang II promotes vasoconstriction, inflammation, and fibrosis via AT1R, whereas signaling through AT2R shows contrasting effects. Furthermore, ACE2 cleaves Ang II into Ang(1-7), which acts through the Mas receptor and MrgD to exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects while modulating autophagy and oxidative stress.
Why it matters
Understanding the opposing arms of the pulmonary renin-angiotensin system highlights specific therapeutic targets, particularly enhancing the ACE2/Ang(1-7)/Mas axis, to mitigate pathological extracellular matrix deposition in pulmonary fibrosis.
Limits
The abstract describes a non-systematic narrative review providing no quantitative synthesis, effect sizes, or study quality assessments. Clinical applicability, patient characteristics, and safety outcomes of targeting these pathways are not reported.
Cited by
- supports ACE2 balances angiotensin II and angiotensin-(1-7), reducing pro-oxidative products and increasing antioxidant products.