1) COVID-19, ACE2 DEPLETION AND RAMPANT ANG II OVEREXPRESSION: A DISEASE OF LOCAL AND SYSTEMIC RAS
The great puzzle of COVID-19 may finally be solved. The immense number of systems involved, and the vast number of symptoms presented can be explained by the implication of Systemic
2) and Local Renin-Angiotensin Aldosterone (RAS) systems.
The RAS systems (both local (non-Renin dependent) and systemic (Renin-dependent) are primarily responsible for fluid homeostasis, most notably blood pressure regulation. However, the RAS system has evolved over time to
3) be responsible for far, far more than just fluid homeostasis. Everything we are seeing in COVID-19, both acute and in its sequelae, can be explained by the overexpression of a single peptide: Angiotensin II. This peptide, necessary to maintain a healthy blood pressure, is kept
4) in check by ACE2, which cleaves it into ANG 1-7. Without this process, the body will experience organ damage (fibrosis), rampant inflammation, neurodegeneration, senescence and even telomere shortening. Again, all that we are observing in COVID-19.
5) INFLAMMATION AND ENDOTHELIAL DYSFUNCTION
A large number of experimental studies have shown that Ang II mediates several key events of the inflammatory processes. Inflammation involves activation of the endothelium of blood vessels and expression of diverse endothelial cell
6) selectins that dictate extravasation of specific leukocyte populations to the site of injury.
Ang II also promotes endothelial dysfunction through COX-2 activation, which generates vasoactive prostaglandins and ROS. Moreover, Ang II favours the recruitment of infiltrating
7) inflammatory cells into tissues by stimulating the production of specific cytokine/chemokines. For example, Ang II induces the production of the potent monocyte chemoattractant MCP-1 in cultured monocytes.
HEART FAILURE AND CARDIAC DISEASE
It is widely known that increased
8) ANG II expression causes CHF. This is why, of course, ACE Inhibitors are used to treat CHF and a variety of cardiac and hypertensive diseases. Renin-angiotensin system (RAS) blockade with angiotensin converting enzyme (ACE) inhibitors and/or angiotensin II type 1 receptor
9) blockers (ARBs) has turned out to be beneficial at all stages of this continuum.
THE CAROTID BODY AND THE OBSERVED “HAPPY HYPOXIA”
The local RAS in carotid body plays a key role in modulating the carotid body response to hypoxia. Angiotensin II itself increases carotid body
10) efferent activity, presumably via activation of the AT1 receptor. Meanwhile, chronic hypoxia upregulates several key RAS components in the carotid body, including time-course dependent ACE activity.
AUTOIMMUNITY
RAS is critically involved in the development of
11) Th1/Th17-mediated multiple sclerosis (MS) as shown in experimental autoimmune encephalomyelitis (EAE), a well-established mouse model for human MS. Peripheral CD4+T cells from EAE mice show increased levels of Ang II which acting through the AT1 receptor promote the
12) synthesis of Th1 and Th17 cytokines, specifically IFN-γ and IL-17.
A recent study also highlighted the role of AT1 receptors in glomerular inflammation associated with autoimmune disease in rodents by studying AT1A receptor-deficient (AT1A−/−) MLR-Faslpr/lpr (lpr) mice,
13) which develop an autoimmune disease resembling human systemic lupus erythematosus (SLE).
NEURODEGENERATION
The discovery of the existence of a paracrine, locally acting RAS operating independently from the circulatory RAS has fostered studies addressing the role of brain RAS,
14) in particular in what concerns its involvement in the pathophysiology of Alzheimer's disease, the most common form of dementia.
Elevated neuronal and perivascular immunoreactivity of ACE and Ang II surrounding the parietal and frontal cortex vessels in the brain of
15) Alzheimer's disease patients has also been reported. Increased ACE activity would be expected to reduce brain perfusion, characteristic of Alzheimer's disease possibly through elevated production of Ang II.
OXIDATIVE STRESS, AGING AND SENESCENCE
We have previously referred to
16) the impact of Ang II in ROS production. In fact, Ang II robustly stimulates the production of molecular oxygen species that trigger mitochondrial dysfunction and cellular injury. Ang II via AT1 receptor stimulation can activate NAD(P)H oxidase to produce ROS, resulting in
17) oxidative stress damage. Harman has proposed that ROS are the most prominent molecular species involved in the aging process. According to his theory, ROS contribute significantly to various age-associated organ failures, including hypertension, cardiovascular diseases and
18) renal damage. Hence, Ang II could be involved in organ senescence given its ability to mediate the release of oxidant species.
The disruption of AT1A receptor preserves mitochondrial and cellular wellness and promotes longevity by modulating ROS production and sirtuin
19) expression.
GLUCOSE INTOLERANCE AND DIABETES
Data indicate the existence of a functional ACE2-angiotensin(1–7)-Mas axis in Caco-2 cell line, which may provide an alternative mechanism for GLUT2 and/or SGLT1-mediated intestinal glucose uptake in normal and diabetic conditions.
20) Levels of ANG II and the presence of ACE2 Autoantibodies must be tested for in all those exposed toi the spike protein.
journals.sagepub.com/doi/10.1177/17…
link.springer.com/chapter/10.100…
embopress.org/doi/full/10.10…

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More from @Parsifaler

17 Nov
1) LESSONS FROM THE PAST INTENTIONALLY SUPPRESSED: PRE SARS-CoV-2 KNOWLEDGE OF ACE2, ITS FUNCTIONS AND THE SARS-CoV SPIKE PROTEIN
To begin with, please read the following paragraph:
To further clarify whether the intraperitoneally injected Spike-Fc protein directly affected lung
2) pathology in mice, we examined the localization of the injected Spike-Fc protein in lung. Spike-Fc was detected in lung homogenates by western blot using human Fc–specific antibody, whereas injected control-Fc was not detected. In addition, using immunohistochemistry, we found
3) that Spike-Fc protein localized to bronchial epithelial cells, inflammatory exudates and alveolar pneumocytes. Notably, Spike-Fc primarily localized to severe lesions. This localization of Spike-Fc protein is similar to Spike antigen staining in SARS-CoV–infected mice.
Read 17 tweets
16 Nov
1) THE LOSS OF ACE2 RESULTS IN THE ULTRA-RAPID DEVELOPMENT AND PROGRESSION OF ACUTE AND CHRONIC AGE-RELATED DISEASES
If one were to be an enemy of humanity and wished to end the lives of as many people as possible and in the stealthiest way possible and could choose only one
2) protein to remove from the body to accomplish this task – that protein would certainly be ACE2.
The loss of ACE2 causes a massive upregulation of Angiotensin II. This hormone is involved in all the pathologies of aging. Microvascular disease, cancer, neurodegeneration, heart
3) disease, sudden death and immune dysfunction.
GROUND GLASS OPACITIES/LUNG INJURY
As an immediate concern, it is thought that the upregulation of ANG II is responsible for the ventilation-perfusion mismatch seen in COVID-19: We hypothesize that hypoperfusion of apparently
Read 19 tweets
15 Nov
1) IS COVID-19 A DISEASE OF INDUCED DNA AND MASSIVE FREE RADICAL DAMAGE WHEREIN CLINICAL SYMPTOMS ARE ACTUALLY A “POST-VIRAL SYNDROME?” THERE IS NO “ASYMPTOMATIC SPREAD” AS THE MAIN PHASE OF “SYMPTOMATIC COVID-19” OCCURS WITHIN THE TRANSCRIPTOME.
Before COVID-19, the medical
2) community spoke of anosmia, in relation to viruses, as post viral olfactory loss.
If we look at lung radiation damage (not in the context of actual radiation, but in context of the massive amounts of free radicals, which it generates) we see a direct parallel to the lung
3) findings of COVID-19. Ionizing radiation produces reactive oxygen species that induce lesions, and not only is tumor tissue damaged, but overwhelming inflammatory lung damage can occur in the alveolar epithelium and capillary endothelium. Is this not COVID-19?
Read 8 tweets
11 Nov
peptides besides angiotensin I and thereby affects diverse physiological functions, including renal development and male reproduction. In addition, ACE has a role in both innate and adaptive responses by modulating macrophage and neutrophil function — effects that are magnified
when these cells overexpress ACE. Macrophages that overexpress ACE are more effective against tumours and infections. Neutrophils that overexpress ACE have an increased production of superoxide, which increases their ability to kill bacteria. These effects are due to increased
ACE activity but are independent of angiotensin II. ACE also affects the display of major histocompatibility complex (MHC) class I and MHC class II peptides, potentially by enzymatically trimming these peptides. Understanding how ACE expression and activity affect myeloid cells
Read 4 tweets
11 Nov
1) MY MOST IMPORTANT WORK TO DATE:
THE SPIKE PROTEIN ITSELF INDUCES RAAS HYPERACTIVATION VIA “CHRONIC ANG II INFUSION”
EVERYTHING IS A DECOY. WE HAVE BEEN FOCUSED ON THE PRESENCE OF THE SPIKE PROTEIN (THE INSTIGATOR). YET, IT IS THE ABSENCE OF ACE2 THAT IS ALL OF COVID-19 AND ImageImageImage
2) ITS SEQUELAE.
COVID-19 IS A DISEASE OF OVEREXPRESSED ANG II: ACE2 DEGRADING/DOWNREGULATION BY THE SPIKE PROTEIN RESULTS IN PRIMARY ARTERIAL HYPERTENSION, MICROVASCULAR DISEASE AND DNA DAMAGE
THE SPIKE PROTEIN CAUSES HUMANS TO “SELF-INJECT” THEMSELVES WITH ANG II. JUST AS IS
3) DONE IN LAB MICE EXPERIMENTS
Let us begin by looking at one of those very lab mice experiments using ANG II. In C57BL/6-mice equipped with osmotic mini pumps, delivering AngII in four different concentrations between 60 ng/kg per min and 1 μg/kg per min during 28 days,
Read 20 tweets
9 Nov
Apologies for sounding the alarm again today, but given my research of the past 24 hours, it is far, far worse than I thought it was yesterday.
1) BEYOND PULMONARY ARTERIAL HYPERTENSION: THE SPIKE PROTEIN INDUCES SYSTEMIC MICROVASCULAR DISEASE, SIMILARLY AFFECTING ALL ORGANS
2) THIS IS COVID-19 OF THE S PROTEIN (WITHOUT THE IMMEDIATELY PATHOLOGICAL AND DELETERIOUS EFFECTS OF THE E PROTEIN (ARDS INDUCING))
PLEASE SEE MY PREVIOUS POST FOR LUNG INVOLVEMENT
I believe the small vessel damage and endothelial tissue remodeling, which are hallmarks of
3) Pulmonary Arterial Hypertension, are also occurring in all major organs.
HEART
To understand what I believe is happening, let us first look at Small Vessel Disease. Small vessel disease is a condition in which the walls of the small arteries in the heart aren't working
Read 17 tweets

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