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Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

nature.com

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Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#31

Post by ptest1 »

CapriciousCptl wrote: post #26

__ This is not medical advice. Do not go out and take a bunch of losartan without a doctor, you could die. __ Here's the article's main point (from 2005): Kuba et al showed that by injecting losartan into mice (a common ACE inhibitor that is off patent) with a SARS-Coronavirus protein leads to less lung injury than the controls without losartan. No studies have shown this works in living, breathing humans, but... (Or…

This wasn’t in a petri dish actually, this was an in vivo study using mice. Other in vivo studies show similar.

There are actually no known trials with ARBs and SARS-CoV-2, which is really weird. There should be. One reason why is because most of the non-crazy (eg Chinese medicine) drugs being trailed were selected by semi-brute force from in vitro type testing. ARBs wouldn’t work in vitro AFAICT, which is a reason they haven’t been tested; the drug won’t stop the virus from entering cells the same way other drugs might, but instead may stop some or all of the major damage the virus does to the body.

There’s lots of discussion and papers collected here on this subject:

https://twitter.com/__philipn__

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#32

Post by CapriciousCptl »

ptest1 wrote: post #31
CapriciousCptl wrote: post #26

__ This is not medical advice. Do not go out and take a bunch of losartan without a doctor, you could die. __ Here's the article's main point (from 2005): Kuba et al showed that by injecting losartan into mice (a common ACE inhibitor that is off patent) with a SARS-Coronavirus protein leads to less lung injury than the controls without losartan. No studies have shown this works in living, breathing humans, but... (Or…

This wasn’t in a petri dish actually, this was an in vivo study using mice. Other in vivo studies show similar. There are actually no known trials with ARBs and SARS-CoV-2, which is really weird. There should be. One reason why is because most of the non-crazy (eg Chinese medicine) drugs being trailed were selected by semi-brute force from in vitro type testing. ARBs wouldn’t work in vitro AFAICT, which is a reason t…

Thanks, corrected my comment. I'd also expect observational studies since ace-inhibitors are so widespread.

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#33

Post by ptest1 »

noipv4 wrote: post #27

ARB stands for AT1R blockers ( angiotensin II type one ) and they represent a major class of antihypertensive medications. These drugs end in sartan. They will not block ACE2 which is a protein which gets expressed in the lung tissues. Please Do not get carried away. https://en.wikipedia.org/wiki/Angiotensin-converting_enzyme_...

They won’t block ACE2 but as indicated in the article they may prevent the lung damage associated with SARS by blocking AT1R which is the receptor that may mediate lung damage.

There’s lots of discussion and papers collected here:

https://twitter.com/__philipn__

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#34

Post by _bxg1 »

rolph wrote: post #24
_bxg1 wrote: post #23

Can we get a (2005)?

there is a difference between tech and science with regard to correlations between recency and quality. Scientific articles gain credibility as they age and no known exception to elucidated principles is apparent. in this case the [2005] article is superior to a [2020] article. i do agree however it is helpful and conventional to include a date of publication

People reading quickly might mistake it for being about the current Coronavirus. The date would help rule that out.

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#35

Post by seieste »

rolph wrote: post #16
pezo1919 wrote: post #12

How can I find it out if I have high ACE2?

having high ACE2 is not something that you need to worry about as you only need enough to get the virus in you. - having "high" ACE2 could actually be a benefit if it turns out that you retain proper ACE2 functionality after infection and through the course of the physiological challenge of the virus.

This seems to be in contradiction of other published results. Can you provide a source?

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#36

Post by rolph »

_bxg1 wrote: post #34
rolph wrote: post #24

Earlier quoted context omitted.

there is a difference between tech and science with regard to correlations between recency and quality. Scientific articles gain credibility as they age and no known exception to elucidated principles is apparent. in this case the [2005] article is superior to a [2020] article. i do agree however it is helpful and conventional to include a date of publication

People reading quickly might mistake it for being about the current Coronavirus. The date would help rule that out.

for all intents and purposes it is about the current coronavirus. regardless of drift the viral peplomer is still being used to dock with the ACE2 receptor protien and still uses a small sequence region to bind the receptor.

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#37

Post by ptest1 »

rolph wrote: post #10
epmaybe wrote: post #6

Earlier quoted context omitted.

Another interesting side effect could be other temporizing measures in the inpatient setting. My understanding from a brief skim of older research papers is that the ACE inhibitors and angiotensin receptor blockers that we use today, like lisinopril or losartan, could upregulate the expression of ACE-2 receptors. If a patient is admitted with coronavirus, discontinuing blood pressure medications such as lisinopril an…

this is something of a bush to beat around. - when the virus docks with the ACE2 receptor there is a loss of the ACE2 receptor function as it is a destructive process. - when the virus inhabits the cell there is probably a cytoplasmic down regulation of ACE2 expression as the cell is now "claimed" as a place for replication so the question would be when would we administer or withdraw such an ACE2 blocker the loss of…

I wrote a long comment and it got deleted, argh!

Best guess? ACE2 loss is probably bad, having more ACE2 probably doesn’t drive disease severity:

https://twitter.com/__philipn__/status/1229568317167243264?s...

Relative ace2 reduction correlates w disease severity; viral load growth the same between groups - check out study!

Chinese paper discusses this as well:

https://pubmed.ncbi.nlm.nih.gov/32061198-inhibitors-of-ras-m...

They reason that 1) ARB doesn’t increase ACE2 past normal human baseline anyway, just to normal status 2) Younger have higher ACE2, older women more than older men; both groups more protected so disease severity unlikely from higher ACE2.

ACE2-fc being developed- will both stop AT1R activation and neutralize virus:

https://twitter.com/robertlkruse/status/1233986542097567744?...

He is looking for funding if any funders are reading this. Comment here and I can connect.

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#38

Post by rolph »

seieste wrote: post #35
rolph wrote: post #16

Earlier quoted context omitted.

having high ACE2 is not something that you need to worry about as you only need enough to get the virus in you. - having "high" ACE2 could actually be a benefit if it turns out that you retain proper ACE2 functionality after infection and through the course of the physiological challenge of the virus.

This seems to be in contradiction of other published results. Can you provide a source?

could you please provide citations and the contradictions?

Re: Angiotensin converting enzyme 2 (ACE2) crucial in SARS-coronavirus lung injury (2005)

#39

Post by ptest1 »

seieste wrote: post #35
rolph wrote: post #16

Earlier quoted context omitted.

having high ACE2 is not something that you need to worry about as you only need enough to get the virus in you. - having "high" ACE2 could actually be a benefit if it turns out that you retain proper ACE2 functionality after infection and through the course of the physiological challenge of the virus.

This seems to be in contradiction of other published results. Can you provide a source?

As far as I can tell, there are no studies showing a higher ACE2 causes more severe disease. Sure, it could, but the pathophysiological models and animal data suggest that it is the loss of ACE2 that may drive disease severity.

There is a contradictory preprint (that hasn’t passed peer review) on ACE2 mRNA expression in smokers’ lungs being higher than non-smokers; but there is data saying the opposite happens in animal models of mice exposed to smoke:

https://pubmed.ncbi.nlm.nih.gov/20178811-losartan-attenuates...

There is also an inaccurate preprint on ethnic groups and ACE2 expression with a low n count which also didn’t pass peer review.

ACE2 loss is probably bad, having more ACE2 probably doesn’t drive disease severity:

https://twitter.com/__philipn__/status/1229568317167243264?s...

Relative ace2 reduction correlates w disease severity; viral load growth the same between groups - check out study! Chinese paper discusses this as well:

https://pubmed.ncbi.nlm.nih.gov/32061198-inhibitors-of-ras-m...

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