are you aware of, the role vitamin D plays in the ACE2 and renin-angiotensin system?
- [Dr.
Seheult] : obviously plays an important role in regulating blood pressure
and fluid homeostasis, and, you know, I think even in the lungs too.
But what's interesting about the vitamin D renin-angiotensin system kind of
it converges on the ACE2 receptor, which, as you know, and probably
most of the world has heard by now is how the SARS-CoV-2 virus enters into
ourselves, it binds that receptor.
Well, what's been shown with SARS-CoV-1 is when the virus which also binds
to the same receptor to get inside of the cell, it binds to the receptor
and it internalizes the receptor and down-regulates ACE2, which is
not good because that is really important for this renin-angiotensin
regulation, as you know, Dr.
Seheult.
So that's been shown with SARS-CoV-1.
And what happens when the ACE2 gets down-regulated, acute
lung injury gets really bad.
And so there's been some animal studies that have found, for example, if you
high-dose with the active form of vitamin D, the animals, and then you
cause acute lung injury, ACE2 goes down, acute lung injury goes up in
the placebo group, but the vitamin D group, it normalizes the ACE2 levels.
So if you think about it, you know, this is a hypothesis, of course, another
potential way vitamin D could be playing an important role in this specific
virus is through regulating ACE2 levels.
And what's interesting is that there was just a very recent study that came out.
ACE2, the gene, it's located on the X chromosome.
And women have two X chromosomes most of the time.
One of those X chromosomes, the gene is inactivated.
But there are genes that escape that.
And ACE2 is one of those.
And so women have much higher levels of ACE2.
And so researchers are thinking this is protecting them from a more severe
COVID-19 outcome because they're getting that ACE2 levels, like,
you know, higher in terms of, you'd think, Oh, well, more ACE2, that
means the virus is getting in and, but actually, biology always tricks you.
You know, you always think one thing, and then it's like this beautiful,
you know, sort of complex scenario.
But I'm digressing.
And I just, kind of, wanted to bounce it off you because you're such a scholar,
and I thought you probably would find that interesting, and I certainly hope
scientists are testing that hypothesis because it seems very relevant.
- [Dr.
Seheult] : Yeah, it does.
Not only that, the human body is so complex as you say that
there's so many connections.
The other aspect of angiotensin or ACE2 I should say is that it gets
rid of pro-oxidative products and it increases antioxidant products.
So for instance, angiotensin II, and angiotensin [1-7], those are in balance
and ACE2 tries to keep those in balance.
But when ACE2 is knocked out by other SARS-CoV-2 or SARS 1, the amount of
oxidative stress goes up dramatically.
And what we see that that may play a role in terms of thrombosis.
So you have oxidative stress in the ACE2 receptors at the endothelium
of the vasculature that causes inflammatory stress, oxidative
stress, that causes thrombosis.
And that's where that happens as well.
So all of these things, it seems as though we've got the dots,
connecting them requires very good randomized controlled trials.
But again, like you said, hypothesis driving type of studies
that may answer that question.