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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.
WALTER M CHESNUT
JUL 7

尖峰蛋白和PIEZO1：损害内皮，诱发致命的心律失常，脱髓鞘轴突和启动肿瘤

在这里，我们又有一个例子，说明仅Spike蛋白如何诱发多种致命病理。

沃尔特·M·栗子

https://open.substack.com/pub/wmcresearch/p/the-spike-protein-and-piezo1-damaging

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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.

I cannot do this without your support. My research is funded only by Paid Subscription to this Substack and Direct Donation. Currently (7/7/25), of the 14K Subscribers to this Substack, only 361 are Paid Subscribers. Great thanks to the two new Paid Subscribers since Friday. It is an important goal to have a total of 700 Paid Subscribers for sustainabilit 穗蛋白和压电1：损害内皮，诱导致命的心律失常，脱髓鞘和起始肿瘤在这里，我们还具有秒杀蛋白单独诱导多种致命病症的另一个例子。 沃尔特M Chesnut 7ul 7在Covid-19中的内皮压电1中的应用程序潜在角色阅读。 所有所需的是一次接触尖刺蛋白。 这就是诱导内皮延长损伤所需的一切。 我不能压力足以让Covid视为“只是感冒”是一个严重的错误。 此外，您不知道令人难以置信的令人难以置信的是，这种病毒蛋白已成为数十亿人的基因 - 多次。 最近的临床前研究提供了第一次暴露于SARS-COV-2的尖刺蛋白或受体结合结构域的第一次暴露的令人信服的证据，足以促使对肺血管内皮的急性对损伤。 通过压电1和储存钙通道的上调和激活发生这种损害，导致细胞内钙浓度增加。 了解Covid-19相关内皮功能障碍：压电1作为潜在治疗目标https://… Piezo1是机械活化的离子通道蛋白，其意味着它响应于触摸，压力或拉伸细胞膜的物理力而打开。 或者，如上所述的尖峰蛋白。 机械机构，机械力转化为电化学信号的过程[1]，是许多生物过程的关键因素，包括触感和疼痛感，血压调节和细胞稳态[[2]，[3]，[4]，[5 机械调整的主要机制已经建立了几十年前的机械敏感离子通道的识别和表征[6]。 尽管如此，这些渠道的分子形式仍然难以忽视，直到PataPoutian和同事的压电渠道的开创性发现[7]。 随后对Piezo系列，Piezo1和Piezo2的两个成员的研究已经为哺乳动物机械调节的分子基础和生物学意义提供了宝贵的见解[8]。 虽然到目前为止，Piezo2主要是与机械囊[[9]，[10]，[11]，[12]，[13]，[14]，[15]]，压电1特异性地脱颖而出，作为有希望的药物发育的治疗靶标。 它广泛表达于多种细胞类型[16]，并且涉及各种（Patho）生理过程，例如血管发育[17]，骨重塑[18]，以及肿瘤进展[19]等。 caizo1及其抑制剂：概述和观点https://www…我们已经从一开始就讨论了sp 然而，如果我们在尖刺蛋白激活激活这种离子通道蛋白质的能力时，我们开始看到一种血清的病理证据。 这是什么证据表明了？ 尖刺蛋白的激活压电1导致比“只是”损害内皮更大的伤害。 例如，穗蛋白的激活可以是最近突然心脏死亡剧烈浪涌的驱动因素之一，因为压电1的活化可以诱导致命的心律失常。 重要的是要注意，尖峰蛋白确实影响了与类似于轻度心脏病发作的时尚的心脏。 除了SR（Sarcoplasmic网状物）Ca2 +摄取功能障碍外，CA2 +过载触发器也从SR中触发自发性CA2 +泄漏。 鉴于SR中的Ryr2即使在舒张压[CA2 +] I中，CA2 +将泄漏SR，导致细胞内CA2 +波的发生，使CA2 +超出原始网站和ELICITS ARR的蔓延 我们的数据说明了MI促进Ryr2的磷酸化后的压电1激活，这证明了改变Ryr2的感觉，并增加舒张性SR Ca2 +泄漏[34]。 潜在机制可归因于CAMKII的PIEZO1增强活性，这对磷酸化Ryr2至关重要，并有助于RYR2的进一步稳定化[35,36]。 在细胞水平下，压电1激活通过显着缩短APD和诱导EADS触发心律源重塑，并在动作电位的第3阶段后期发生。 缩写APD允许来自SR的正常CA2 +释放。 然而，当[Ca2 +]我保持上升至膜电位对于Na + / Ca2 +交换器（NCX）的平衡电位负阴性时，Incx将被激活，引起膜去极化。 这些晚期EADS与包括心房心动过速，VT和心室颤动的心动过缓临床相关[37]。 根据我们的数据，可以在Piezo1的持续但不是渐逝激活的持续但不是渐变的激活下看到由连续EADS定义的触发活动。 此外，作为非选择性阳离子通道，Piezo1也进行Na +流入。 因此，升高的细胞内Na +可以激活NCX的反向模式以增加[Ca2 +] I [38]。 总之，上述推迟指出了在MI之后与压电1cko小鼠相关的心律失常发生的可能机制。 心脏puezo1通过在心肌梗塞HTTPS://… +处理连接机械应力，通过将机械应力与Ca2 +处理联系起来，加剧了致死的心间血致肿瘤 它也是一个后Covid疫苗接种现象。 本研究确定了Covid-19疫苗接种后CNS脱髓鞘并发症。 Covid-19疫苗接种可能导致CNS并发症，可能与疫苗接种后炎症过程相连。 COVID-19疫苗接种后CNS脱髓鞘综合征：案例系列https://…这可能是真的。 然而，我建议除了罪魁祸首之外或代替炎症过程，穗蛋白的Piezo1的激活肯定是原因。 压电1在脱髓鞘和轴突变性中的作用。 （a）轴突中的压电1通道的激活负面调节CNS Myelination。 Yoda1在轴突中的压电1通道的激活促进了细胞外Ca2 +进入神经元的流入，又触发了er的Ca2 +诱导（CICR）。 这有助于CNS轴突的脱髓鞘。 GSMTX4阻断PieZo1活动并防止脱髓鞘（57）。 （b）压电1激活抑制轴突再生。 在轴突损伤时，用Camkii-NoS-PKG途径（58）募集压电1升高到生长锥中并抑制轴突再生。 Piezo1频道在多发性硬化HTTPS://…PueC9513475 / PieN的新兴作用 我们还有另一种机制，尖刺蛋白可以诱导涡轮癌。 Piezo1转换驱动肿瘤的产生的信号。 它还有助于创造这些肿瘤生长和传播所需的情况。 作为机械传导的关键组分，据报道，压电1控制生理和病理过程，例如先天免疫，骨形成和各种癌症[119]。 Piezo1转换驱动肿瘤发生的机械损伤信号。 反过来，在肿瘤进展期间不断改变机械力可以通过改变压电1表达进一步影响疾病的结果。 Piezo1在大多数肿瘤中高度表达，并与预后差（表1）呈正相关（表1）。 重要的是，Piezo1与癌症标志密切相关[44]。 在一起，压电1是潜在的肿瘤的生物标志物和预测因素; 此外，它是潜在的抗肿瘤治疗靶标。 机械敏感离子通道Piezo1信号在癌症霍尔标记中：结构和功能https://www…幸运的是，我正在研究的Piezo1的天然抑制剂，并将写一篇讨论它们的帖子。 显然，这是必须立即停止尖刺蛋白mRNA的另一个原因。 衷心感谢您的读者，对话和支持。 而且，就像我总是州一样，没有你的支持，我不能这样做。 你让我继续前进。 我会继续战斗。 请有一个幸福的一周。 没有你的支持，我不能这样做。 我的研究仅由支付认购本食盒和直接捐赠资助。 目前（7/7/25），14K订阅者对此家喻户口，只有361个是支付用户。 非常感谢自星期五的两个新的付费订阅者。 这是共有700名可持续发展的重要目标