8 ms·

For you know if the ACE2 genes mentioned with relation to coronavirus have anything to do with ACE inhibitors and ARB inhibitors?

by pkaye 7y ago

wbl 7y ago
ACE is the enzyme that ACE inhibitors inhibit. Why is it expressed in the lungs? I have no clue.
- deleted 7y ago
  [deleted]
- epmaybe 7y ago
  That's where Angiotensin I (ACE = Angiotensin Converting Enzyme) is converted to Angiotensin II, which acts on tons of blood vessels to increase blood pressure. That's essentially why ACE inhibitors have a blood pressure effect. On top of that, Bradykinin is an inflammatory mediator that is degraded by ACE. It's heavily implicated in the side effect ACE inhibitors have of dry cough.
  - wbl 7y ago
    But why the lungs and not the liver?
    - epmaybe 7y ago
      Now that is a very interesting question! Unfortunately, I don't think that we have a complete answer. A couple of notes, that perhaps can provide some perspective: 1. lungs are highly vascularised areas with a large amount of vascular endothelium, making them a great location to express ACE if you want to convert as much angiotensin I as you can in the space of a heartbeat (which you'd like to do if your blood pressure dropped, for example). 2. ACE is not specific for angiotensin, it acts on a variety of peptides. Bradykinin is a good example as it can provide more perspective on why ACE is expressed mainly in lung tissue. Bradykinin acts to contract smooth muscle in your airways. Thus, degrading bradykinin via ACE is a good way to improve your breathing.
jokowueu 7y ago
Your are correct It's related to ACE inhibitors .
philipn 7y ago
It is related, but it's pretty complicated. For some information on this and the potential relationship, see my twitter account: https://twitter.com/__philipn__ https://twitter.com/__philipn__
forkexec 7y ago
The latest is that ACE2 and TMPRSS2 are both needed to infect humans. There are already two compounds identified to block these pathways, one of which is already a medication used in Japan. Both are very safe with huge LD50's.
- pkaye 7y ago
  So would there be an additional risks from coronavirus to those taking ACE or ARB inhibitors?
  - ignoramous 7y ago
    See a recent albeit heated discussion here: https://news.ycombinator.com/item?id=22500063 https://news.ycombinator.com/item?id=22500063
dreamcompiler 7y ago
IIRC, conventional ACE inhibitors don't inhibit ACE2, which would be be needed to fight COVID-19.
fxtentacle 7y ago
Apparently, a serine protease inhibitor works. I didn't hear anything about regular ace inhibitors. https://www.dpz.eu/en/home/single-view/news/die-vermehrung-von-sars-coronavirus-2-im-menschen-verhindern.html https://www.dpz.eu/en/home/single-view/news/die-vermehrung-v...
delhanty 7y ago
This may be relevant: there's a recent (3rd March) hypothesis due to Rami Sommerstein from Department of Infectious Diseases, Bern University Hospital [0] that ACE inhibitors are a potential risk factor for fatal Covid-19 in those patients taking ACE inhibitors for hypertension/diabetes/cardiovascular disease: >The largest Chinese study with 44,672 confirmed cases of Covid-19 shows a high overall case fatality rate (CFR) of 2.3% [2]. Important co-morbidities are hypertension (CFR 6.0%), diabetes (CFR 7.3%), cardiovascular disease (CFR 10.5%) and age >70 (CFR 10.2%) [2]. Similar co-morbidities were noted for the SARS outbreak in 2003. > ... >On the one hand, it has been shown that the Covid-19 agent (also known as SARS-CoV-2), uses the SARS-COV receptor angiotensin converting enzyme (ACE) 2 for entry into target cells [4]. The interface between ACE2 and the viral spike protein SARS-S has been elucidated and the efficiency of ACE2 usage was found to be a key determinant of SARS-CoV transmissibility [4]. > >On the other hand, it could be shown in animal experiments that both the ACE-inhibitor lisinopril and the angiotensin-receptor blocker losartan can significantly increase mRNA expression of cardiac ACE2 (5-fold and 3-fold, respectively) [5]. Further, losartan also significantly increases cardiac ACE2 activity [5]. Edit: thank you philipn for your twitter link. [0] https://www.bmj.com/content/368/bmj.m810/rr-2 https://www.bmj.com/content/368/bmj.m810/rr-2
- philipn 7y ago
  Please see my twitter account for lots on this. I'm in contact with a bunch of top researchers on this topic (renin-angiotensin system; ACE2/Ang 1-7/Mas axis; ARB usage for viral diseases) and will be posting a summary update soon: https://twitter.com/__philipn__/status/1235756671852589056 https://twitter.com/__philipn__/status/1235756671852589056 It may be the other way around: ACEi/ARB may be protective. HTN without ACEi/ARB would be non-protective, potentially so much so that it skews the group fatality numbers. This is because people with HTN have a different renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially less ACE2. This is being looked at now. But the key is that in every study ever done on viral lung disease, etc, AT1R blockade was highly beneficial, and we know that ACE2-knockout basically screws up lungs, makes viral lung disease way worse, etc. Please see my twitter posts. The virus eats up ACE2, downregulating it as it binds. This would have delirious effects. Check out the linked "essential reading" twitter post. Will be posting a summary to my twitter soon.

For you know if the ACE2 genes mentioned with relation to coronavirus have anything to do with ACE inhibitors and ARB inhibitors?

by pkaye 7y ago

For you know if the ACE2 genes mentioned with relation to coronavirus have anything to do with ACE inhibitors and ARB inhibitors?

wbl 7y ago

ACE is the enzyme that ACE inhibitors inhibit. Why is it expressed in the lungs? I have no clue.

deleted 7y ago
[deleted]
epmaybe 7y ago
That's where Angiotensin I (ACE = Angiotensin Converting Enzyme) is converted to Angiotensin II, which acts on tons of blood vessels to increase blood pressure. That's essentially why ACE inhibitors have a blood pressure effect. On top of that, Bradykinin is an inflammatory mediator that is degraded by ACE. It's heavily implicated in the side effect ACE inhibitors have of dry cough.
- wbl 7y ago
  But why the lungs and not the liver?
  - epmaybe 7y ago
    Now that is a very interesting question! Unfortunately, I don't think that we have a complete answer. A couple of notes, that perhaps can provide some perspective: 1. lungs are highly vascularised areas with a large amount of vascular endothelium, making them a great location to express ACE if you want to convert as much angiotensin I as you can in the space of a heartbeat (which you'd like to do if your blood pressure dropped, for example). 2. ACE is not specific for angiotensin, it acts on a variety of peptides. Bradykinin is a good example as it can provide more perspective on why ACE is expressed mainly in lung tissue. Bradykinin acts to contract smooth muscle in your airways. Thus, degrading bradykinin via ACE is a good way to improve your breathing.

jokowueu 7y ago

Your are correct It's related to ACE inhibitors .

philipn 7y ago

It is related, but it's pretty complicated. For some information on this and the potential relationship, see my twitter account: https://twitter.com/__philipn__ https://twitter.com/__philipn__

forkexec 7y ago

The latest is that ACE2 and TMPRSS2 are both needed to infect humans. There are already two compounds identified to block these pathways, one of which is already a medication used in Japan. Both are very safe with huge LD50's.

pkaye 7y ago
So would there be an additional risks from coronavirus to those taking ACE or ARB inhibitors?
- ignoramous 7y ago
  See a recent albeit heated discussion here: https://news.ycombinator.com/item?id=22500063 https://news.ycombinator.com/item?id=22500063

dreamcompiler 7y ago

IIRC, conventional ACE inhibitors don't inhibit ACE2, which would be be needed to fight COVID-19.

fxtentacle 7y ago

Apparently, a serine protease inhibitor works. I didn't hear anything about regular ace inhibitors. https://www.dpz.eu/en/home/single-view/news/die-vermehrung-von-sars-coronavirus-2-im-menschen-verhindern.html https://www.dpz.eu/en/home/single-view/news/die-vermehrung-v...

delhanty 7y ago

This may be relevant: there's a recent (3rd March) hypothesis due to Rami Sommerstein from Department of Infectious Diseases, Bern University Hospital [0] that ACE inhibitors are a potential risk factor for fatal Covid-19 in those patients taking ACE inhibitors for hypertension/diabetes/cardiovascular disease: >The largest Chinese study with 44,672 confirmed cases of Covid-19 shows a high overall case fatality rate (CFR) of 2.3% [2]. Important co-morbidities are hypertension (CFR 6.0%), diabetes (CFR 7.3%), cardiovascular disease (CFR 10.5%) and age >70 (CFR 10.2%) [2]. Similar co-morbidities were noted for the SARS outbreak in 2003. > ... >On the one hand, it has been shown that the Covid-19 agent (also known as SARS-CoV-2), uses the SARS-COV receptor angiotensin converting enzyme (ACE) 2 for entry into target cells [4]. The interface between ACE2 and the viral spike protein SARS-S has been elucidated and the efficiency of ACE2 usage was found to be a key determinant of SARS-CoV transmissibility [4]. > >On the other hand, it could be shown in animal experiments that both the ACE-inhibitor lisinopril and the angiotensin-receptor blocker losartan can significantly increase mRNA expression of cardiac ACE2 (5-fold and 3-fold, respectively) [5]. Further, losartan also significantly increases cardiac ACE2 activity [5]. Edit: thank you philipn for your twitter link. [0] https://www.bmj.com/content/368/bmj.m810/rr-2 https://www.bmj.com/content/368/bmj.m810/rr-2

philipn 7y ago
Please see my twitter account for lots on this. I'm in contact with a bunch of top researchers on this topic (renin-angiotensin system; ACE2/Ang 1-7/Mas axis; ARB usage for viral diseases) and will be posting a summary update soon: https://twitter.com/__philipn__/status/1235756671852589056 https://twitter.com/__philipn__/status/1235756671852589056 It may be the other way around: ACEi/ARB may be protective. HTN without ACEi/ARB would be non-protective, potentially so much so that it skews the group fatality numbers. This is because people with HTN have a different renin-angiotensin system profile: more AT1R, less AT2R, more ACE, potentially less ACE2. This is being looked at now. But the key is that in every study ever done on viral lung disease, etc, AT1R blockade was highly beneficial, and we know that ACE2-knockout basically screws up lungs, makes viral lung disease way worse, etc. Please see my twitter posts. The virus eats up ACE2, downregulating it as it binds. This would have delirious effects. Check out the linked "essential reading" twitter post. Will be posting a summary to my twitter soon.