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What Does RAAS do?

The Renin–Angiotensin–Aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance. R R

Kidney cells convert Prorenin which is already in the blood into renin that gets converted into angiotensin I by angiotensinogen, released by the liver. R

Angiotensin (ANG) is converted into Angiotensin 2 (ANGII) by the Angiotensin Converting Enzyme (ACE). R

Now ANGII can either bind to Angiotensin II 1 Receptor (AT1R) or Angiotensin II 2 Receptor (AT2R). R

What About With Covid?

We know that covid binds to Angiotensin Converting Enzyme 2 (ACE2).

ACE2 binding and going into the cell via replication creates lots of spike. R

Spike is toxic to endothelium causing endothelium to open up. R

Neutrophils and monocytes cause hyperinflammation and platelets thrombosis, along with the stickiness from agglunation (the sticking of red blood cells together). R

The continued replication of spike/ACE2 binding continue feedback loops for replicating and leaves the person leaky, inflamed, and depleted of NO/redox capacity. R

ACE2

After loss of ACE2 there is a lot of inflammation from ANGII binding to AT1R. R

Why Does Spike Cause Gut Issues and Dysbiosis?

Recent studies show that there is a crosstalk between the gut microbiome and the cardiovascular system. R

Gut microbiota-derived molecules may affect the vascular system by directly on the blood vessels and the heart. R

Through multilateral signalling, the cardiovascular system and gut microbiota communicate altering the structure and function of bacterial habitat, i.e., intestines. R

It has been found that gut bacteria may affect the circulatory system indirectly by modulating gut sympathetic activity and RAS. R

In this regard, both the sympathetic nervous system and RAS are key factors contributing to numerous cardiovascular pathologies, including hypertension and heart failure. R

For example, Short-chain fatty acids (SCFA), such as butyrate, acetate or propionate - affect blood pressure by modulating local RAS in the kidneys:

• Sodium butyrate inhibits angiotensin II-induced hypertension by suppressing the (pro)renin receptor and the intrarenal RAS) R

• Acetate supplementation also resulted in the downregulation of the local RAS in the kidney and heart R

• Succinate (an intermediate in microbial propionate synthesis) can activate of the renal RAS through the SUCNR1 signaling R

• Indoxyl sulfate (a gut bacteria-derived uremic toxin) - may cause chronic kidney injury by activating intrarenal RAS R

So essentially, having RAAS issues, esp. with AT1R can cause an gastric issues and dysbiosis affecting the byproducts the your healthy bacteria normally make. R

Post-Covid Cough & Shortness of Breath

Many people I know, after the acute bout of covid have a persistent cough.

Some of them have been given diagnoses of asthma (with inhalers and immunosuppressants) or others feel like they can’t breath in all the way.

This is because the AT1R receptors in the lungs are activated by ACE2 loss. R

You may have guessed, repeated infections or chronic loss of ACE can eventually lead to scarring in the lungs and even more inflammation as the tissue in the lungs tries to remodel towards some kind of homeostasis. R

RAAS in POTS

Patients with POTS have increased plasma levels of Ang II, despite inappropriately low renin and aldosterone on the background of low blood volume. R

Some patients with POTS have reduced ACE2 activity and reduced adrenal responsiveness. R

These findings support the hypothesis that abnormal angiotensin regulation contributes to the pathophysiology of POTS in some patients. R

ACE2 Levels In Men vs Women

You may have if men or women are more susceptible to covid or long covid.

Well men are more susceptible to covid than women, because they have more ACE2 for entry. R R

This is a double edged sword, because this makes them more likely to bounce back their ACE2 levels after getting covid. R R

Women having less ACE2 naturally don't bounce back as easily which increases susceptibility of long covid. R R

In acute illness, men are more effected, as oestrogen stimulates the immune system against viruses and can reduce the ACE2 mRNA. R

Ways To Increase ACE2

Let's talk about ways to increase ACE2.

Some of my favorite ways are with:

1. Butyrate (as well as butyramide) R R R

2. Melatonin - Post on melatonin R

3. Avoiding spiking blood sugar as glucose downregulates ACE2 R

4. Metformin R

5. Resveratrol R

6. Vitamin B3 (Niacin) R

7. Vitamin D (apelin dependent and independent) R R

8. Intermittent fasting

9. Curcumin

10. Rosmarinic acid (t-cell balance)

11. Alpha lipoic acid (vitamin c + ala)

12. Fish Oil (by increasing apelin) R

13. CBD (decreases ACE2 binding levels but helps ACE2 by increasing apelin) R R

14. NAC

15. Losartan

Stay away from (technical):

1. high-concentration glucose causes ACE2 downregulation by miR-125b R

2. Brg1-FoxM1 protein complex binds to the ACE2 promoter, leading to inhibition of ACE2 transcription R

3. hif1a R

4. tnfa R

5. ERRα - suppresses ACE2 transcription by binding to the ACE2 promoter, leading to higher blood pressure in the kidney R

6. EZH2 - induces H3K27me3 binding to the ACE2 promoter, leading to downregulation of ACE2 gene expression R

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