Angiotensin-converting enzyme 2 regulates autophagy in acute lung injury through AMPK/mTOR signaling

2019 ◽  
Vol 672 ◽  
pp. 108061 ◽  
Author(s):  
Xiaomiao Zhang ◽  
Jian Zheng ◽  
Yunqi Yan ◽  
Zheng Ruan ◽  
Yijiang Su ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Mtor Signaling ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

scholarly journals Angiotensin-Converting Enzyme 2 Improves Arterial Hypoxemia in Meconium-Induced Acute Lung Injury in Piglets

2015 ◽  
Vol 2015 ◽  
pp. 1-7
Author(s):  
Benedikt Treml ◽  
Alexander Loeckinger ◽  
Axel Kleinsasser ◽  
Elisabeth Schoepf ◽  
Ralf Geiger ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Gas Exchange ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Blood Gas ◽  
Meconium Aspiration ◽  
Angiotensin Converting Enzyme 2 ◽  
Partial Pressures

Objective. Meconium aspiration induces acute lung injury (ALI) in neonates born through meconium-stained amniotic fluid. As yet, there is no specific therapy for improving the outcome. Recently, angiotensin-converting enzyme 2 (ACE2), which inactivates angiotensin II (Ang II), has been shown to ameliorate murine ALI. Design. To evaluate the therapeutic potential of this substance, we studied ACE2 in a piglet model of ALI induced by meconium aspiration. Subjects. Twelve anesthetized piglets were subjected in an animal research laboratory. ALI was induced by tracheal meconium instillation. Thereafter, six animals were randomly assigned to the ACE2 group, while another 6 served as control. Measurements. Systemic, pulmonary hemodynamic, and blood gas exchange parameters and Ang II levels were examined before ALI induction and at various time points after administering ACE2 or saline. In addition, ventilation-perfusion distribution of the lung was assessed by the multiple inert gas elimination technique (MIGET). Main Results. Animals treated with ACE2 maintained significantly higher arterial partial pressures of oxygen (Pao2) and lower arterial partial pressures of carbon dioxide (Paco2), respectively. Furthermore, Ang II, which was substantially increased, returned to basal values. Conclusion. In summary, ACE2 improves blood gas exchange in meconium-induced ALI in piglets.

scholarly journals Angiotensin-Converting Enzyme 2 Inhibits Apoptosis of Pulmonary Endothelial Cells During Acute Lung Injury Through Suppressing SMAD2 Phosphorylation

2015 ◽  
Vol 35 (6) ◽  
pp. 2203-2212 ◽  
Author(s):  
Yong Ji ◽  
Fengying Gao ◽  
Bo Sun ◽  
Jing Hao ◽  
Zhenwei Liu
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Cell Apoptosis ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Pulmonary Endothelial Cells ◽  
Smad2 Phosphorylation ◽  
Induced Apoptosis

Background/Aims: Angiotensin converting enzyme 2 (ACE2) has an established role in suppressing the severity of acute lung injury (ALI), especially when it was applied together with transplantation of human umbilical cord mesenchymal stem cells (uMSCs). Although the effects of ACE2 in ALI are believed to mainly result from its role in hydrolyzing angiotensin II (AngII), which subsequently reduces the vascular tension and subsequent pulmonary accumulation of inflammatory cells, we and others have recently reported a possible role of ACE2 in suppressing the ALI-induced apoptosis of pulmonary endothelial cells. However, the underlying mechanisms remain undetermined. Methods: Here, we analyzed the alteration in lung injury severity in ALI after ACE2, by histology and inflammatory cytokine levels. We analyzed apoptosis-associated proteins in lung after ALI, as well as in cultured endothelial cells treated with nitric oxide (NO). We overexpressed SMAD7 to inhibit SMAD2 signaling in cultured endothelial cells and examined its effects on NO-induced cell apoptosis. Results: ACE2 alleviated severity of lung injury after ALI. ACE2 significantly decreased the ALI-induced apoptosis of pulmonary cells in vivo, and ACE2 protected endothelial cells against NO-induced apoptosis in vitro. NO induced phosphorylation of a key factor of transforming growth factor β (TGF β) receptor signaling, SMAD2, which could be dose-dependently inhibited by ACE2. Inhibition of SMAD2 phosphorylation through expression of its inhibitor SMAD7 significantly inhibited NO-induced cell apoptosis, without need for ACE2. Conclusion: Our data suggest that ACE2-mediated AngII degradation may inhibit AngII-mediated SMAD2-phophorylation, possibly through a TGFβ-independent manner, which subsequently suppresses the ALI-induced cell death. Our results thus reveal a novel molecular pathway that controls the pathogenesis of ALI.

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