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
4) healthy areas could be a consequence of vasoconstriction due to accumulation of angiotensin II, caused by decreased availability of ACE2, and that these changes in vascular resistance lead to a shunt or steal of vascular flow towards areas of non-aerated hyperperfused lung in
5) moderate to severe COVID-19 cases. Further studies are needed to investigate ventilation-perfusion abnormalities and whether these could be explained by the local increase in angiotensin II.
SUDDEN CARDIAC DEATH
Rats harboring the human renin and angiotensinogen genes (dTGR)
6) feature angiotensin (ANG) II/hypertension-induced cardiac damage and die suddenly between wk 7 and 8. We observed by electrocardiogram (ECG) telemetry that ventricular tachycardia (VT) is a common terminal event in these animals.
IMMUNE DYSFUNCTION
The potential for
7) angiotensin II to directly modulate inflammatory cell functions was suggested by the observation that human mononuclear leukocytes express specific binding sites for angiotensin II (27). Tsutsumi and associates subsequently demonstrated large numbers of binding sites for
8) angiotensin II in rat spleen and found that these sites were primarily AT1 receptors (26). This is consistent with our receptor autoradiography findings of diffuse AT1-specific binding in mouse spleen. Our studies further show that these are predominantly AT1A receptors and
9) that AT1A receptors are expressed in a variety of splenocyte populations including T cells, macrophages, and B cells.
Complementing its central role in BP homeostasis, the RAS has diverse and complex effects on innate and adaptive immunity. Through coordinated regulation of
10) Ang II levels, the RAS proteolytic cascade affects hemodynamic injury in the heart, kidney, and vasculature leading to profound, global upregulation of inflammatory responses.
ENDOTHELIAL DYSFUNCTION
In the context of an inflammatory process, local activation of RAS and
11) Ang II synthesis both increased vascular permeability by promoting the expression and secretion of VEGF (vascular endothelial growth factor) (Chua et al, 1998; Kitayama et al, 2006; Suzuki et al, 2003), and induced the expression of endothelial adhesive molecules including
12) selectins (P- and L-selectin), vascular cell adhesion molecules-1 (VCAM-1), intercellular adhesion molecules-1 (ICAM-1) and their ligands, the integrins (Alvarez et al, 2004; Piqueras et al, 2000; Pueyo et al, 2000). Ang II also promotes endothelial dysfunction through COX-2
13) activation, which generates vasoactive prostaglandins and ROS (Welch, 2008; Wu et al, 2005).
AUTOIMMUNITY
The recent observation that Ang II modulates T cell responses, suggests a possible role of the peptide in autoimmune diseases. RAS is critically involved in the
14) development of Th1/Th17-mediated multiple sclerosis (MS) as shown in experimental autoimmune encephalomyelitis (EAE), a well-established mouse model for human MS (Platten et al, 2009). Peripheral CD4+T cells from EAE mice show increased levels of Ang II which acting through
15) the AT1 receptor promote the synthesis of Th1 and Th17 cytokines, specifically IFN-γ and IL-17.
NEURODEGENERATION
As evidenced from literature, enzymes and peptides related to RAS are expressed and interact with other RAS components (Renin, Ang I, ACE, Ang II, AT1R and AT2R)
16) in the brain. There is strong evidence for the activation of AngII/AT1R axis in initiating a cascade of events leading to increase in oxidative stress, apoptosis, and neuroinflammation causing neurodegeneration in the several brain disorders.
CANCER
The renin-angiotensin
17) system (RAS) plays an important role not only in homeostasis but also in carcinogenesis. Recent epidemiological studies suggest that hypertensive patients with upregulated systemic RAS functions are at a significantly increased risk for the subsequent development of cancers
18) with poor outcomes, and moreover that RAS inhibitors reduce tumor development, progression, and metastasis.
These hypotheses are coming to light, and just three days ago, a paper suggesting (as I have previously) that soluble ACE2 may be very therapeutic against COVID-19.

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More from @Parsifaler

17 Nov
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 ImageImage
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 Image
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 Image
Read 20 tweets
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 Image
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 ImageImage
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
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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