The Spike Protein and PIEZO1: Damaging the Endothelium, Inducing Fatal Arrhythmias, Demyelinating Axons and Starting Tumors

Here we have yet another example of how the Spike Protein alone can induce multiple fatal pathologies.

Potential roles of endothelial PIEZO1 in COVID-19.

All it takes is one exposure to the Spike Protein. That is all that is needed to induce prolonged damage to the endothelium. I cannot stress enough that viewing COVID as “just a cold” is a grave mistake. Additionally, you have no idea how unbelievably mind-boggling it is that this viral protein has been gene therapied into billions of human beings – multiple times.

A recent preclinical study provides compelling evidence for the first time that a single exposure to the spike protein or receptor-binding domain of SARS-CoV-2 is sufficient to induce acute-to-prolonged damage to pulmonary vascular endothelium. This damage occurs through the upregulation and activation of Piezo1 and store-operated calcium channels, leading to increased intracellular calcium concentrations.

Understanding COVID-19-associated endothelial dysfunction: role of PIEZO1 as a potential therapeutic target
https://pmc.ncbi.nlm.nih.gov/articles/PMC10937424/

What is PIEZO1? PIEZO1 is a mechanically activated ion channel protein, meaning it opens in response to physical forces like touch, pressure, or stretching of the cell membrane. Or, the Spike Protein, as noted above.

Mechanotransduction, the process by which mechanical forces are transformed into electrochemical signals [1], is a key contributor to numerous biological processes, including touch and pain sensation, blood pressure regulation, and cell homeostasis [[2], [3], [4], [5]]. The principal mechanism of mechanotransduction was established decades ago with the identification and characterization of mechanosensitive ion channels [6]. Still, the molecular identities of these channels remained elusive until the groundbreaking discovery of the Piezo channels by Patapoutian and co-workers [7].

Subsequent studies on two members of the Piezo family, Piezo1 and Piezo2, have provided invaluable insights into the molecular basis and biological significance of mammalian mechanotransduction [8]. While Piezo2 has so far mainly been discussed in connection with mechanosensation [[9], [10], [11], [12], [13], [14], [15]], Piezo1 specifically stands out as a promising therapeutic target for drug development. It is widely expressed in multiple cell types [16] and involved in various (patho)physiological processes such as vascular development [17], bone remodeling [18], and tumor progression [19], among others.

Piezo1 and its inhibitors: Overview and perspectives
https://www.sciencedirect.com/science/article/pii/S0223523424003829

Of course, we have discussed from the beginning that the Spike Protein begins its invasion of the body via the endothelium. Yet, if we look more closely at the Spike Protein’s ability to activate this ion channel protein, we begin to see a plethora of pathological evidence. What does this evidence suggest? That the Spike Protein’s activation of PIEZO1 causes far more harm than “just” damaging the endothelium.

For example, the Spike Protein’s activation of PIEZO1 may be one of the drivers of the recent surge in sudden cardiac deaths, as the activation of PIEZO1 can induce lethal arrhythmias. It is important to note that the Spike Protein does, indeed, affect the heart in a fashion similar to a mild heart attack.

In addition to SR (sarcoplasmic reticulum) Ca2+ uptake dysfunction, Ca2+ overload triggers spontaneous Ca2+ leak from SR as well. Given that RyR2 in SR has a finite open probability even at diastolic [Ca2+]i, Ca2+ will leak out of SR, resulting in the occurrence of intracellular Ca2+ waves so that Ca2+ spreads beyond the original sites and elicits arrhythmogenic afterdepolarizations [18]. Our data illustrated that Piezo1 activation after MI promotes the phosphorylation of RyR2, which is evidenced to vary the sensation of RyR2 and increase diastolic SR Ca2+ leakage [34]. Potential mechanism could be attributed from Piezo1-enhanced activity of CaMKII, which is crucial to phosphorylate RyR2 and contribute to a further destabilization of RyR2 [35,36]. At the cellular level, Piezo1 activation triggered arrhythmogenic remodeling through remarkably shortening APD and inducing EADs, which occurs late in phase 3 of action potential. An abbreviated APD permits normal Ca2+ release from SR. However, when the [Ca2+]i keeps rising until the membrane potential is negative to the equilibrium potential for the Na+/Ca2+ exchanger (NCX), INCX will be activated, causing membrane depolarization. These late EADs are clinically relevant with tachycardia including atrial tachycardia, VT, and ventricular fibrillation [37]. In compliance with our data, triggered activity defined by continuous EADs could be seen under the sustained but not evanescent activation of Piezo1. Furthermore, as a nonselective cationic channel, Piezo1 conducts Na+ influx as well. Raised intracellular Na+ could consequently activate the reverse mode of NCX to increase [Ca2+]i [38]. In summary, the above inferences pointed the possible mechanism in the occurrence of arrhythmia linked to Piezo1Cko mice after MI.

Cardiac Piezo1 Exacerbates Lethal Ventricular Arrhythmogenesis by Linking Mechanical Stress with Ca2+ Handling After Myocardial Infarction
https://pmc.ncbi.nlm.nih.gov/articles/PMC10255393/

Demyelination has been observed as a post-COVID phenomenon. It is also a post-COVID vaccination phenomenon.

This study identified CNS demyelination complications after COVID-19 vaccination. The COVID-19 vaccination could result in CNS complications, possibly connected to a post-vaccination inflammatory process.

CNS Demyelination Syndromes Following COVID-19 Vaccination: A Case Series
https://pmc.ncbi.nlm.nih.gov/articles/PMC11000968/

The authors of the above paper posit that the demyelination may be “possibly connected” to an inflammatory process. That may be true. However, I suggest that in addition to or instead of an inflammatory process being the culprit, the Spike Protein’s activation of PIEZO1 could certainly be the cause.

The roles of Piezo1 in demyelination and axon degeneration. (A) The activation of Piezo1 channels in axon negatively regulates CNS myelination. The activation of Piezo1 channels in axon by Yoda1 promotes the influx of extracellular Ca2+ into the neuron which, in turn, triggers Ca2+-induced Ca2+ release (CICR) from ER. This contributes to the demyelination of CNS axons. GsMTx4 blocks Piezo1 activity and prevents the demyelination (57). (B) Piezo1 activation inhibits axon regeneration. Upon axon injury, Piezo1 is recruited to the growth cones and inhibits axon regeneration via the CaMKII-Nos-PKG pathway (58).

The emerging roles of piezo1 channels in animal models of multiple sclerosis
https://pmc.ncbi.nlm.nih.gov/articles/PMC9513475/

There is yet one more pathological state that PIEZO1 activation may cause: that is tumorigenesis. We have yet another mechanism by which the Spike Protein can induce turbocancers. PIEZO1 transduces signals that drive the creation of tumors. It also assists in creating the circumstances necessary for those tumors to grow and spread.

As a critical component of mechanical conduction, Piezo1 has been reported to control physiological and pathological processes, such as innate immunity, bone formation, and various cancers [119]. Piezo1 transduces mechanical damage signals that drive tumorigenesis. In turn, constantly changing mechanical forces during tumor progression can further affect the outcome of the disease by altering Piezo1 expression. Piezo1 is highly expressed in most tumors and positively correlated with a poor prognosis (Table 1). Importantly, Piezo1 is closely related to cancer hallmarks [44]. Together, Piezo1 is a potential biomarker and predictor for tumors; furthermore, it is a potential antitumor therapeutic target.

Mechanosensitive Ion Channel PIEZO1 Signaling in the Hall-Marks of Cancer: Structure and Functions
https://www.mdpi.com/2072-6694/14/19/4955

Is there any good news? Yes. Fortunately, there are natural inhibitors of PIEZO1, which I am researching and will write a post discussing them. Clearly, this is yet another reason that Spike Protein mRNA must be stopped immediately.

Thank you, as always, for your readership, dialogue, and support. And, as I always state, I can’t do this without your support. You keep me going. I will keep fighting. Please have a blessed week.