scholarly journals Angiotensin-converting enzyme 2 deficiency accelerates and angiotensin 1-7 restores age-related muscle weakness in mice

2018 ◽  
Vol 9 (5) ◽  
pp. 975-986 ◽  
Author(s):  
Hikari Takeshita ◽  
Koichi Yamamoto ◽  
Satoko Nozato ◽  
Masao Takeda ◽  
So-ichiro Fukada ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Muscle Weakness ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Age Related

scholarly journals Hypertension and renin-angiotensin system blockers are not associated with expression of Angiotensin Converting Enzyme 2 (ACE2) in the kidney

2020 ◽  
Author(s):  
Xiao Jiang ◽  
James M. Eales ◽  
David Scannali ◽  
Alicja Nazgiewicz ◽  
Priscilla Prestes ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Individual Risk ◽  
Human Tissues ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Age Related ◽  
Renal Expression

Angiotensin converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) - the cause of COVID-19 disease. It has been hypothesized that use of renin-angiotensin system (RAS) inhibiting medications in patients with hypertension, increases the expression of ACE2 and thereby increases the risk of COVID-19 infection and severe outcomes or death. However, the effect of RAS-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. We examined how hypertension, its major metabolic co-phenotypes and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterised by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Collectively, our data indicate that neither hypertension nor antihypertensive treatment are likely to alter individual risk of SARS-CoV-2 infection or influence clinical outcomes in COVID-19 through changes of ACE2 expression. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

scholarly journals Hypertension and renin-angiotensin system blockers are not associated with expression of angiotensin-converting enzyme 2 (ACE2) in the kidney

2020 ◽  
Vol 41 (48) ◽  
pp. 4580-4588
Author(s):  
Xiao Jiang ◽  
James M Eales ◽  
David Scannali ◽  
Alicja Nazgiewicz ◽  
Priscilla Prestes ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Human Tissues ◽  
Converting Enzyme ◽  
Antihypertensive Medications ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Age Related ◽  
Renal Expression

Abstract Aims Angiotensin-converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2)—the cause of coronavirus disease 2019 (COVID-19). However, the effect of renin-angiotensin system (RAS)-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. Methods and results We examined how hypertension, its major metabolic co-phenotypes, and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterized by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Conclusion Our results indicate that neither hypertension nor antihypertensive treatment is likely to alter the expression of the key entry receptor for SARS-CoV-2 in the human kidney. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.

Thermodynamics of the interaction between the spike protein of severe acute respiratory syndrome- coronavirus-2 and the receptor of human angiotensin converting enzyme 2. Effects of possible ligands

2020 ◽  
Author(s):  
Cristina Garcia-Iriepa ◽  
Cecilia Hognon ◽  
Antonio Francés-Monerris ◽  
Isabel Iriepa ◽  
Tom Miclot ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Molecular Mechanisms ◽  
Molecular Design ◽  
Binding Free Energy ◽  
Transmembrane Protein ◽  
Spike Protein ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Rational Molecular Design ◽  
Rational Evaluation

<div><p>Since the end of 2019, the coronavirus SARS-CoV-2 has caused more than 180,000 deaths all over the world, still lacking a medical treatment despite the concerns of the whole scientific community. Human Angiotensin-Converting Enzyme 2 (ACE2) was recently recognized as the transmembrane protein serving as SARS-CoV-2 entry point into cells, thus constituting the first biomolecular event leading to COVID-19 disease. Here, by means of a state-of-the-art computational approach, we propose a rational evaluation of the molecular mechanisms behind the formation of the complex and of the effects of possible ligands. Moreover, binding free energy between ACE2 and the active Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is evaluated quantitatively, assessing the molecular mechanisms at the basis of the recognition and the ligand-induced decreased affinity. These results boost the knowledge on the molecular grounds of the SARS-CoV-2 infection and allow to suggest rationales useful for the subsequent rational molecular design to treat severe COVID-19 cases.</p></div>

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