THE SYSTEMIC REMOVAL OF DEFENSES TO AGE-RELATED DISEASE: THE INDUCTION OF AUTOABS TO AND DOWNREGULATION OF ACE2 (CARDIOVASCULAR DISEASE) AND HLA (AUTOIMMUNITY): INTERACTION WITH p53 (CANCER)

Molecular Mimicry/Interactions of the Spike Protein and Self-Destruction

With this post I wish to explain the mechanisms more fully behind my post of yesterday. As I have discovered, I believe that the same mechanism behind the induction of immunodeficiency is also behind the induction of cardiovascular disease. The Spike Protein has the “interesting” ability to “remove” or interact with three of the most important defenses the body has to the diseases of aging. Those being ACE2 Cardiovascular Disease), HLA (Immune Deficiency) and p53 (Cancer).

ACE2

ACE2 is critical for cardiovascular protection and homeostasis.

ACE2 has emerged as the dominant mechanism for negative regulation of the RAS, by metabolizing Ang II into the beneficial peptide Ang 1–7. This important biochemical and physiological property is being harnessed as potential therapy for HF. Since the discovery of ACE2 in 2000, tremendous progress has been made in elucidating its biochemical actions and its key role in heart disease and HF. ACE2 is widely expressed and regulates the fundamental cellular biology of cardiomyocytes, cardiofibroblasts, and coronary endothelial cells in both HF with reduced ejection fraction and HF-pEF models. Ang 1–7 has also emerged in HF models as a physiologically active peptide with protective effects. Enhancing Ang 1–7 action may also provide marked therapeutic effects in HF. Clinical and experimental studies clearly support a physiological and pathophysiological role for ACE2/Ang 1–7 in HF, and studies indicate that increasing/activating ACE2/Ang 1–7 results in beneficial effects to prevent heart disease and HF.

Role of the ACE2/Angiotensin 1–7 Axis of the Renin–Angiotensin System in Heart Failure
https://www.ahajournals.org/doi/10.1161/circresaha.116.307708

If you read the above paper, you will learn how ACE2 is also involved in the regulation of blood pressure and its beneficial effects on hypertension.

In the presence of the Spike Protein, these protective qualities are diminished, as the Spike Protein downregulates the expression of this essential cardiovascular protector.

Angiotensin converting enzyme 2 (ACE2) as the receptor for SARS-CoV-2 entry, is also an important regulator of renin-angiotensin system (RAS) homeostasis, which plays an unsettled role in the pathogenesis of COVID-19. Here, we demonstrated that SARS-CoV-2 Spike protein activated intracellular signals to degrade ACE2 mRNA.

Spike-mediated ACE2 down-regulation was involved in the pathogenesis of SARS-CoV-2 infection
https://www.journalofinfection.com/article/S0163-4453(22)00404-2/fulltext

Paradoxically, ACE2 is protective in the cardiovascular system, and SARS-CoV-1 S protein promotes lung injury by decreasing the level of ACE2 in the infected lungs.3 In the current study, we show that S protein alone can damage vascular endothelial cells (ECs) by downregulating ACE2 and consequently inhibiting mitochondrial function.

SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2
https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.121.318902

The interaction of the Spike Protein may be causing a long-term downregulation of ACE2 by the induction of autoantibodies most likely induced by the Spike/ACE2 immune complex.

Dynamics of the ACE2–SARS-CoV-2/SARS-CoV spike protein interface reveal unique mechanisms
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449962/

And, indeed, we are observing ACE2 Autoantibodies after COVID. We need research to determine if they are being induced after Spike Protein vaccination.

Many patients with a history of SARS-CoV-2 infection have antibodies specific for ACE2. Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma. Plasma from these patients also inhibits exogenous ACE2 activity. These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of PASC.

Development of ACE2 autoantibodies after SARS-CoV-2 infection
https://pubmed.ncbi.nlm.nih.gov/34478478/

Therefore, we have an acute and chronic downregulation of ACE2, allowing for the development and/or progression of cardiovascular disease.

HLA

HLA (Human Leukocyte Antigen, or Major Histocompatability Complex) is essential for the development of adaptive immunity. In particular, it is essential in “teaching” the body to distinguish between self and non-self. Without HLA, the body’s immune system will behave like a “mad dog” and. Attack. Tissue. Any. Tissue.

This leads to the development of Autoimmunity.

The presence of the Spike Protein also has the “unique” ability to downregulate this critical protein, as well.

It has been published that SARS-Cov-2 patients have fewer NK cells that also display an exhausted phenotype. Here, Bortolotti and al. transfect bronchial epithelial cell line Beas-2B with SP1, SP2 from SARS-CoV-2 or full spike protein form SARS-CoV. SP1 expression alone downregulated classical HLAs in Beas-2B, while GATA3 driven expression of the non-classical HLA-E increased. One of the peptides in SP1 domain is predicted to bind HLA-E specifically. NK cells co-cultured with SP1 expressing Beas-2B upregulate NKG2A, an inhibitory ligand for HLA-E, and exhibit decreased CD107a expression and cytotoxic activity. Additionally, authors show that all spike proteins tested exert chemotactic activity on NK cells.

Sars-Cov-2 Spike 1 protein control Natural killer cells activation via HLA-E/NKG2A pathway
https://www.immunology.ox.ac.uk/covid-19/covid-19-immunology-literature-reviews/sars-cov-2-spike-1-protein-control-natural-killer-cells-activation-via-hla-e-nkg2a-pathway

As with ACE2, SARS-CoV-2 infection appears to be inducing autoantibodies against this vital, protective protein.

We found a high rate of HLA antibody formation in convalescent plasma donors. The frequency of positivity for HLA antibodies for class I, class II, class I and II, and the overall reactivity was 23%, 31%, 46%, and 76%, respectively. The presented data suggest a closed correlation between SARS-CoV-2 virus infection and the development of HLA antibodies in recovered convalescent plasma donors.

SARS-COV-2 Triggers the Development of Class I and Class II HLA Antibodies in Recovered Convalescent Plasma Donors
https://www.karger.com/Article/FullText/524016

We need research to determine if the Spike Protein forms immune complexes with HLA. I can find no studies on the subject.

P53

P53 is the gene which is perhaps the most protective against the development of cancer.

The transcription factor p53 is a crucial tumor suppressor that regulates diverse cellular responses to protect against cancer development.

The Role of p53 Signaling in Colorectal Cancer
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125348/

Once again, the Spike Protein interacts with this additional, critical protector from the diseases of old age. More research is needed to determine the impact on expression.

However, it is known that the nsp3 protein of targets p53 for degradation. This is clearly a potential risk for cancer.

We discuss the mechanisms by which SARS nsp3 protein targets p53 for degradation and we speculate on the significance for Covid-19 pathogenesis and risk of cancer.

Viral strategies for circumventing p53: the case of severe acute respiratory syndrome coronavirus
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924916/

I hope, with this post, to demonstrate how the Spike Protein may be behind the recent excess deaths and the emergence and acceleration of age-related disease. Also, why therapeutics against it must continue to be developed. We may be faced with a constant environmental battle against this deleterious protein.