Coronavirus Pandemic Update 37: The ACE-2 Receptor – The Doorway to COVID-19 (ACE Inhibitors & ARBs)

Welcome to the new MedCram COVID-19 update, You can see the data here. The numbers in the world have begun to exceed the data in China. What I am going to talk about today is what many of you mentioned in the comments Receptor for SARS-CoV-2 virus that causes COVID-19 ACE, 2. Receptor, ACE, 2 receptors are the way viruses enter cells. Ace 2 receptor is an entrance, but it is not just an entrance Today we will discuss what the ACE 2 receptor is, what it can do and why it matters. I started thinking about this a long time ago, but the more I researched it the more complicated and interesting it became. So I want to do some research before telling you what we know so far. This topic reached a key point, because people have different views on the ACE 2 receptor. After all, we also mentioned before Outside the cell, or on the surface of the cell, there is a SARS-CoV-2 virus receptor. The coronavirus that causes COVID-19 Here is a virus. It has projected antennae, Looks like the light of the sun, so we call this virus coronavirus. This is SARS-CoV-2. The coronavirus in 2019. Here is the S protein, we mentioned before The receptor. For this S. Protein is on the cell surface, Especially the lung cells, which are type II, alveolar cells and the cells of the digestive tract

This receptor is called ACE2 it is, important that you understand. Ace S. Protein is linked to the cell. Here There is another protein called serine protease. This protein is also on the cell membrane. Serine proteases help viruses enter cells. It allows messenger rNA here to enter and infect cells. The key here is that the protein on the side of the cell is ACE 2 and he happens to be the receptor for the SARS-CoV virus in 2002. Why is this a big problem? Data from some animal tests indicate Angiotensin receptor blockers, (, ARBs). This is a very common high blood pressure, medicine And angiotensin-converting enzyme, inhibitors, (, ACEIs). Another common hypertension medicine Can increase the concentration of ACE 2 receptors on the cell surface. So how do you know if you are taking ARB or ACEI Generally ARB ends with “-tan”? These are tank-end angiotensin receptor blockers, (, ARBs). We will explain their role further If they can really increase ACE2 levels. Obviously, if there are more ACE2 receptors on your cell surface, you have more entrances for the virus to enter your cells. Angiotensin-Converting enzyme, inhibitors, (, ACEIs), usually end with “-pril”, Captopril, Enalapril, etc.

These ingredients may also increase ACE 2 receptor concentration. So what should be done for patients who are taking ARB and ACEI People with a history of hypertension appear to have a higher mortality rate, So this led to many people in the papers and on social networks discussing whether we should change the medicine for hypertension. This is an article published on The Lancet on March 11. 2020. The question here is whether patients with hypertension and type 2 diabetes have a higher risk of COVID-19 infection. This article discusses cardiovascular disease, SARS-CoV virus SARS-CoV-2 virus and the ACE 2 protein, which are the virus receptor. This article mentions how ACE inhibitors and ARBs increase ACE expression. Increased expression of ACE 2 will promote COVID-19 infection. Therefore, we hypothesized that the use of ACE2 stimulants to treat diabetes and hypertension increases the risk of developing severe and fatal COVID-19. This is only a hypothesis, and if this hypothesis is proven, it will lead to a contradiction regarding treatment, Because ACE2 reduces inflammation and is proposed as a potential new treatment for inflammatory lung disease, cancer, diabetes and hypertension. Another aspect that should be studied is increased risk of SARS-CoV-2 infection due to genetic susceptibility. This may be due to ACE2 polymorphism. Here they mention that “. We believe that patients with heart disease, hypertension or diabetes using a drug containing ACE2, are at higher risk of developing a severe COVID-19 infection. Therefore, patients should be monitored for ACE2-modulating drugs such as ACE, inhibitors or ARBs. We have not found any evidence that calcium channel blocker antihypertensive drugs increase the expression or activity of ACE 2, So these may be suitable alternative treatments for these patients. Here we have an article published in a mainstream journal. This is a wake-up call for millions of patients who are using these drugs. They assume that these patients are at risk. This view has caused some sensation. The question is whether this is supported by facts. So lets take a look at your reactions. Here is a response from the European College of Cardiology Due to social media related magnification Patients and their doctors. Taking these medications for hypertension are becoming increasingly worried. In some cases they have stopped taking ACE-I or ARB drugs. This is an official response from the European College of Cardiology. There is no reliable scientific basis or evidence to support the speculation of the safety of ACE-I and ARB related to the treatment of COVID-19. In fact, there is evidence from animal trials that these drugs may protect. Against severe pulmonary complications caused by COVID-19 infection, No human data. To date, The European Cardiology Association’s Hypertension Committee wishes to highlight that in the context of the COVID-19 epidemic, there is no evidence that ACE-I and ARB have a deleterious effect. The Hypertension Committee strongly recommends that physicians and patients continue with conventional antihypertensive therapy, Because there is no clinical or scientific evidence that treatment with ACE-I or ARB should be discontinued due to COVID-19 infection. So what kind of treatment is right For further research? We will use some molecular biology, Sometimes it’s a little complicated but not overly complicated. So please be patient and listen to me, sort out what SARS-CoV-2 and renin-angiotensin system do To understand. First, we start with a hormone called angiotensin. It is converted into angiotensin. I abbreviated AT-I. This is done by an enzyme called renin produced by the kidneys Angiotensin. I is then converted into angiotensin II. This is done in the lungs by angiotensin, converting enzyme, (ACE, ) ACE, converts, angiotensin I to angiotensin II in the lungs. We can inhibit ACE through ACE inhibitors. This is the drug that ends with “-pril” such as captopril, lisinopril, etc.

Angiotensin II is a very powerful vasoconstrictor. It also stimulates the adrenal glands to produce aldosterone, reduces potassium and increases sodium concentration, Which raises blood pressure. Angiotensin II is a major demarcation point Because the human body has two states. We call this low state. We call this high state. There are some proteins on the top of the cell membrane. Ace 2 is one of them When there is not much angiotensin II. Angiotensin receptor, I (ATR-I) on the catalytic side of ACE 2 Angiotensin II is converted by ACE 2 Angiotensin 1-7. Understanding. Angiotensin 1-7 is important Because angiotensin 1-7 causes vasodilation And reduce inflammation. This is a good thing. You can also put an angiotensin receptor blocker To stop this process. This is an ARB, So we mentioned angiotensin receptor, blockers And angiotensin-converting enzyme inhibitors. If your angiotensin II is high, Your situation will be like this. You will still have ACE 2, but a high level of angiotensin II will separate the angiotensin receptor from ACE 2

When this happens, when angiotensin II and angiotensin receptor I interact, Can cause blood vessels to contract Can raise high blood pressure, Increased vascular permeability resulting in pulmonary edema and possible acute respiratory distress syndrome. Also, when angiotensin II is high, Our hypothesis is that the gap in ACE 2 allows the coronavirus S protein to bind to ACE 2. The binding here also requires a serine protease Abbreviated as TMPRSS2. This can be suppressed by something called carmostat mesylate Trial. Now, Interestingly, when your angiotensin II is high, This whole complex can be degraded into lysosomes. Let’S quickly, review Angiotensin is converted to angiotensin I by renin Angiotensin, converting enzyme, (ACE, ), converts angiotensin I to angiotensin II Angiotensin-converting enzyme inhibitors can stop this process. If you have too much angiotensin II, It is possible that this angiotensin receptor blocker is separated from ACE 2. It can be activated causing vasoconstriction, increasing hypertension, increasing vascular permeability, causing pulmonary edema and acute respiratory distress syndrome. This is what we don’t want to see in viral pneumonia. However, when the level of angiotensin II is low, It will be metabolized by ACE. 2 Is then converted into angiotensin 1,7, which relaxes the blood vessels

It looks like angiotensin receptor blockers can keep this complex together Block the catalytic side with angiotensin receptors. This can be achieved with angiotensin receptor blockers. If angiotensin II is high, this combination will separate According to assumptions. This allows the virus to bind to ACE 2 and cause degradation. What happens if people do not have ACE? What happens if we take away ACE2 People have actually experimented with mice. They removed the gene responsible for making ACE2 during reproduction. A process called knockout Double knockout means that they removed both the father and mother’s ACE2 gene. So when the mouse was born, the mouse had no ACE 2 at all.

They found that the mice were immune to the virus because they had no receptors, But at the same time, in these mice with ACE 2 removed, they found These mice have worse results in viral pneumonia. Their heart contraction weakens They have elevated levels of angiotensin II. This makes sense because ACE 2 breaks down when angiotensin II is low. This is ACE 2 knockout mouse. This is exactly what we see in patients infected with coronavirus. They saw it in a SARS-CoV mouse virus model in 2002, Decreased ACE 2 levels in these virus models. They have normal ACE levels but lower ACE 2 levels. They also saw elevated levels of angiotensin II When they give mice, ARB and ACE inhibitors Test results have improved. I will put links to these studies in the description box below In the case of respiratory syncytial virus. They gave recombinant ACE 2 to mice and found that the results were better, So you can see from the animal hypothesis, If you add an ACE inhibitor, He inhibits angiotensin converting enzyme Keep angiotensin II on the low side. What we might see is that these angiotensins are actually on the high side. You will predict if angiotensin II is on the high side Can produce aldosterone, low, sodium and high blood pressure. This is what they see in very severe COVID-19 patients. Their sodium levels are very low and the most critical condition is very high blood pressure before the collapse. You can also see here that, based on this hypothesis, angiotensin receptor blockers may improve the situation, Diastolic blood vessels and anti-inflammatory. I want to emphasize that, although we have data for mice for humans, we don’t see these things happen Not at least in plasma, not in free ACE. We do not know how it is at the organizational level. This phenomenon is still possible. So what I want to emphasize here is that these are hypotheses derived from various studies over the past 20 years. This may be what happened If you are interested in this type of research, I will put a lot of links in the description column. It seems to me now that, if we are going to tell you to stop using angiotensin receptor blockers and angiotensin converting enzyme inhibitors In my humble expert opinion, if you think I am an expert, I would support the point of view of the European Society of Cardiology. We don’t know now, and we have some animal tests suggesting they might be protective. There are some reports of COVID-19 deaths, Their vasoconstriction was normal on admission, But for days with viral myocarditis or because of the conditions we see here, Their blood vessels contracted drastically. This is also what we can expect after seeing the decline in ACE 2 levels. So this is an open question. We can’t draw conclusions until we finish our research. The good news is based on what I’ve seen in the last few days. There are studies on getting patients to start using angiotensin receptor blockers, (ARB). The above is a very long explanation of recent emerging claims. I think we should continue to explore the issue of this receptor, Especially when we discuss vaccines, because ACE 2 will play a very important role in the future treatment of COVID-19. Thanks for watching