The angiotensin-converting enzyme 2/angiotensin (1–7)/mas axis protects against pyroptosis in LPS-induced lung injury by inhibiting NLRP3 activation

2020 ◽  
Vol 693 ◽  
pp. 108562
Author(s):  
Haihua Huang ◽  
Jin Wang ◽  
Zhenwei Liu ◽  
Fengying Gao
Keyword(s):  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

scholarly journals Do sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression explain increased severity and mortality of COVID-19 in males?

Diagnosis ◽  
2020 ◽  
Vol 7 (4) ◽  
pp. 385-386 ◽  
Author(s):  
Jens Vikse ◽  
Giuseppe Lippi ◽  
Brandon Michael Henry
Keyword(s):  
Mortality Rate ◽  
Severe Acute Respiratory Syndrome ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Sars Coronavirus ◽  
Immunomodulatory Treatment ◽  
Angiotensin Converting Enzyme 2 ◽  
Cytopathic Effects ◽  
Severe Lung

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2), shares similarities with the former SARS outbreak, which was caused by SARS-CoV-1. SARS was characterized by severe lung injury due to virus-induced cytopathic effects and dysregulated hyperinflammatory state. COVID-19 has a higher mortality rate in men both inside and outside China. In this opinion paper, we describe how sex-specific immunobiological factors and differences in angiotensin converting enzyme 2 (ACE2) expression may explain the increased severity and mortality of COVID-19 in males. We highlight that immunomodulatory treatment must be tailored to the underlying immunobiology at different stages of disease. Moreover, by investigating sex-based immunobiological differences, we may enhance our understanding of COVID-19 pathophysiology and facilitate improved immunomodulatory strategies.

Recombinant angiotensin-converting enzyme 2 improves pulmonary blood flow and oxygenation in lipopolysaccharide-induced lung injury in piglets

2010 ◽  
Vol 38 (2) ◽  
pp. 596-601 ◽  
Author(s):  
Benedikt Treml ◽  
Nikolaus Neu ◽  
Axel Kleinsasser ◽  
Christian Gritsch ◽  
Thomas Finsterwalder ◽  
...  
Keyword(s):  
Blood Flow ◽  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Pulmonary Blood Flow ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

scholarly journals Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury

2012 ◽  
Vol 90 (6) ◽  
pp. 637-647 ◽  
Author(s):  
G. J. Rey-Parra ◽  
A. Vadivel ◽  
L. Coltan ◽  
A. Hall ◽  
F. Eaton ◽  
...  
Keyword(s):  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2

scholarly journals Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease

2020 ◽  
Author(s):  
Joseph W. Golden ◽  
Curtis R. Cline ◽  
Xiankun Zeng ◽  
Aura R. Garrison ◽  
Brian D. Carey ◽  
...  
Keyword(s):  
Lung Injury ◽  
Transgenic Mice ◽  
Angiotensin Converting Enzyme ◽  
Small Animal ◽  
Infection Model ◽  
Converting Enzyme ◽  
Male Mice ◽  
Health Crisis ◽  
Angiotensin Converting Enzyme 2 ◽  
Female Mice

ABSTRACTThe emergence of SARS-CoV-2 has created an international health crisis. Small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection due to low affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promotor. In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals revealed increases in transcripts involved in lung injury and inflammatory cytokines. In the lower dose challenge groups, there was a survival advantage in the female mice with 60% surviving infection whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared to female mice. This is the first highly lethal murine infection model for SARS-CoV-2. The K18-hACE2 murine model will be valuable for the study of SARS-CoV-2 pathogenesis and the assessment of MCMs.

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 Subtyping meconium protease activities which degrade lung protective angiotensin converting enzyme-2 in human lung cells

2021 ◽  
Vol 8 (3) ◽  
pp. 113-118
Author(s):  
Naisha Chokshi ◽  
Amal Abdul-Hafez ◽  
Bruce D Uhal
Keyword(s):  
Lung Injury ◽  
Angiotensin Converting Enzyme ◽  
Protease Inhibitors ◽  
Proteolytic Enzymes ◽  
Critical Role ◽  
Negative Regulator ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Human Lung Cells

Purpose: Meconium pneumonitis occurs due to local lung injury and inflammation in newborn with meconium aspiration. The activation of Renin Angiotensin System (RAS) plays critical role in lung injury. Angiotensin converting enzyme-2 (ACE 2) functions as a negative regulator of the angiotensin system by converting pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. Our previous study has shown that meconium causes degradation of lung protective ACE-2 by proteolytic enzymes present in meconium. However, the specific proteases in meconium that degrade ACE-2 have not yet been identified.  Objective: To begin characterizing ACE-2-degrading proteases in meconium through the use of different subtypes of protease inhibitors. Methods: Alveolar epithelial A549 cells were exposed to F-12 medium, 2.5% meconium and meconium + specific protease inhibitors (PIs). Specific PIs used included chymostatin, AEBSF(Pefobloc) and leupeptin. At the end of incubation, cell lysates were collected for ACE-2 immunoblotting and enzyme activity. Results: Reduction of ACE-2 immunoreactive 100-115 kDa bands or enzymatic activity by meconium was attenuated by treatment with chymostatin, but not with the other the PIs.  These data suggest the involvement of cysteine-like proteases in meconium in ACE-2 degradation, and suggest a potential therapeutic strategy of PI administration to babies aspirating meconium.

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