ACE2 inhibition leads to pulmonary fibrosis

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.

本综述阐述了ACE-2如何通过影响多种因素，包括成纤维细胞成分、促炎细胞因子以及缺氧等，在导致肺纤维化损伤中发挥有害作用。当ACE2的活性受到抑制时，血管紧张素II（Ang II）转化为Ang-(1-7)的过程无法得到恰当促进。因此，促炎的Ang II水平上升，而抗炎的Ang-(1-7)水平下降。值得注意的是，ACE2的抑制已被观察到会导致Ang II肽水平上升，这些肽是Ⅰ型血管紧张素受体（AT1R）的配体。这一现象被视为肺纤维化、血管收缩、内皮功能障碍和细胞死亡的重要风险因素。