As a real visionary, Jean-Marc Sabatier* emphasizes the essential role of the renin-angiotensin system in the occurrence of many pathologies. Little known until now, “this hormonal system is everywhere, and it controls everything,” he says. The interview.

Jean-Marc Sabatier (DR)

What is the renin-angiotensin system (RAS), the dysfunction of which you believe is the cause of many diseases?

It is the most important physiological regulatory system in our body; it controls autonomic, renal, pulmonary, and cardiovascular function. It also controls innate immunity and various microbiota (including gut microbiota). It is a cascade of endocrine and enzymatic regulation. This ubiquitous system is found in all organs and tissues of the human body.

You were the first to demonstrate that a dysfunctional RAS underlies Covid-19 disease. What’s new today?

Indeed, I see that all pathologies in the human body arise as a result of a malfunction of this key body system, unless these pathologies are related to genetic abnormalities. This goes far beyond Covid-19. To understand this, it is necessary to take into account the genetic polymorphism of the actors (ligands and receptors) of ASD, its evolution during a person’s life (ASD in an infant is different from ASD in a child, an adult, and the elderly), it develops from birth to death. Due to its omnipresence in the body at the level of organs, tissues and cells, it controls all functions related to the life of cells. This global “vision” of the importance of ASD in full control over the human body, as well as in the potential launch of various pathologies, is new. Researchers will certainly gradually discover the extreme importance of the RAS, this hormonal system that has been misnamed because it was originally identified in the kidney and liver (hence its name), while finally being present in all organs. It controls all the vital functions of the body.
The binding of the SARS-CoV-2 coronavirus (or spike protein) to its cellular receptor ACE2 (angiotensin-converting enzyme 2) prevents the degradation of angiotensin 2 by ACE2, which in excess causes excessive activation of the cellular receptor AT1R. Excessive activation of ASD has a very negative effect on the body, in particular, it leads to the development of COVID-19 diseases. AT1R receptor has vasoconstrictor (hypertensive), proinflammatory (cytokine storm), prothrombotic, profibrotic, prooxidative (causes oxidative stress), proangiogenic effect, hypertrophy of organs (heart, lungs, etc.), inhibits the production of nitric oxide (NO), which affects immune and nervous system… Overactivated AT1R receptor (= RAS dysfunction) is the real culprit in Covid-19 diseases.

This is a visionary approach to science…

Yes, I am waiting for what I believe will become obvious to researchers only after several decades of extensive research: the occurrence of autoimmune diseases and cancers due to RAS dysregulation (except for genetic diseases). All these diseases have one thing in common: widespread RAS. It is the key to all non-genetic pathologies, the conductor of the functions of the human body, not the brain, as is commonly believed today. Because the brain itself is controlled by the RAS. It controls the function of neurons and other cells of the nervous system. It is the supreme leader in our body. This central role of the Russian Academy of Sciences is still unknown today. This will probably be revealed late, in the next few decades, given the complexity of this hormonal system and the relatively slow progress of science in this area of ​​research.

How did you come to that conclusion?

This hormonal system is ubiquitous. That is, it is ubiquitous in various tissues and organs of the human body, including our cells, where it has endocrine activity. For example, in cells, RAS is found on the inner membrane of mitochondria, on the nuclear membrane, and on other membranes of intracellular organelles, so there is no known equivalent in other physiological systems. Why is RAS so ubiquitous in the body? Because he controls everything. It should be everywhere.
It should be noted that there are also such variants of ASD that correspond to the adaptation of this system to a certain function of the organ. For example, RAS in the heart is not the same as RAS in the lungs. There is also a specific RAS in the brain, gut, etc. The same receptors and ligands are always involved, but their share and distribution in tissues are not the same. Thus, local ASD adapts to the function of the organ. Thus, we point to the main system that controls the entire human body. And finally, no one has yet identified him as such!

Does accounting for ASD dysfunction lead to better treatment of the pathologies it causes?

If problems related to ASD dysfunction are solved, it is theoretically possible to treat various (non-genetic) pathologies observed in humans: nervous pathologies (Alzheimer’s disease, Parkinson’s disease, etc.), autoimmune diseases (multiple sclerosis, rheumatoid arthritis, etc.). ), cancer (ASD controls cell proliferation), etc. Its involvement in the functioning of the human body goes, in my opinion, far beyond what is currently described. Its ubiquity in intracellular organelles, including mitochondria, indicates that it is key to cellular function, leading me to say today that it likely underlies all non-genetic pathologies. RAS also plays a role in human longevity. In particular, it works on DNA repair and telomere integrity (structures located at the end of chromosomes involved in longevity).

How can it be targeted?

Medicine now treats mainly the effects, not the causes, of diseases. In order to cure various human pathologies (and mammalian pathologies in general), regardless of their nature, in my opinion, it is necessary to target the renin-angiotensin system. This should make it possible to modulate the potentially harmful effects of an overactivated RAS on the body.
I would like to emphasize the importance of this research area, which is still largely unknown, because I strongly believe that in the coming decades, researchers will discover the crucial role of RAS in the functioning of the body and related pathologies. I strongly encourage researchers and clinicians to take an interest in this area of ​​unexpected potential, especially in therapeutics. This should certainly lead to major advances in applied medicine for the benefit of patients.

*Jean-Marc Sabatier is Director of Research at CNRS and holds a PhD in Cell Biology and Microbiology and an HDR in Biochemistry. Editor-in-Chief of international scientific journals: “Coronaviruses” and “Infectious Diseases – Drug Targets”. He speaks for himself.

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