There and Back Again: How the Spike Protein Induces an Endothelium <> Mitochondria Feedback Loop of Mutual Destruction

A Preprint online today offers insight into uniting two major Spike Protein pathologies.

Proposed mechanisms of induction of the mitochondrial dysfunction as a result of the combined effect of perfusion disturbances which are already shown in Figure 1 and an insufficient rise of the Na+ /K+ -ATPase activity in skeletal muscle. Mitochondrial dysfunction impairs perfusion via ROS and favors itself by lowering the Na+ /K+ -ATPase activity via ROS and low ATP. The poor energetic situation leads to the excessive production and spillover of vasoactive algesic mediators that can reach every organ to cause symptoms and induce hypovolemia. ED: endothelial dysfunction. 

As readers of my Substack are aware, I published a post on October 9^th which discussed the “mitochondrial carpet bombing” induced by the presence of the Spike Protein in the Endothelium.  

https://wmcresearch.substack.com/p/mitochondrial-carpet-bombing-the 

As I referenced in that post: 

On top of that, intratracheal administration of the spike-expressing pseudovirus induced direct damage of lung endothelium by impairing mitochondrial function. Alterations in mitochondrial metabolism in human microvascular endothelial cells caused by the spike protein were accompanied by exuberant production of coagulating factor Xa, with obvious clinical implication for the hypercoagulable state observed in convalescent and severely ill COVID-19 patients. Data are available showing that the spike proteins of different SARS-CoV-2 variants, namely the Wuhan and Delta strains, induced transcriptional upregulation of tissue factor (TF), increased the expression and secretion of coagulating factor V, thrombin, and fibrinogen, and inhibited TF pathway inhibitor (TFPI), the primary regulator of the extrinsic pathway of blood coagulation, in human lung microvascular endothelial cells. 

SARS-CoV-2 and the spike protein in endotheliopathy 
https://www.cell.com/trends/microbiology/fulltext/S0966-842X(23)00189-0 

The paper published today further elucidates how the damage to the vasculature induces a feedback loop of mutual damage to the mitochondria. 

Finally, we explain how mitochondrial dysfunction affects perfusion to close another vicious cycle of mutual triggering. Mitochondrial dysfunction produces ROS to cause endothelial dysfunction and to promote endothelial cell inflammatory, activation of coagulation, and adhesivity. The latter enhances vasoconstrictor influences and favors microcirculatory flow disturbances to further impair perfusion. Finally, via low ATP levels and the generation of ROS that inhibit Na+ /K+ - ATPase and, via an anaerobic metabolism that produces more protons to raise intracellular sodium by the NHE1, mitochondrial dysfunction favors itself. The energetic disturbance is not severe enough to cause organ damage but limits a rise in physical and mental performance (exercise intolerance). Even worse, at a certain level of exercise, the individual post-exertional malaise threshold (PEM) threshold, intracellular sodium in skeletal muscle rises to reach the reverse mode threshold of the NCX. This causes calcium overload to trigger and renew mitochondrial damage. Thus, during exercise the functional damage reproduces itself, keeping the patients captured in a vicious cycle from which they can hardly escape. 

Microvascular Capillary and Precapillary Cardiovascular Disturbances Strongly Interact to Severely Affect Tissue Perfusion and Mitochondrial Function in ME/CFS Evolving from the Post COVID-19 Syndrome 
https://www.preprints.org/manuscript/202312.0791/v1 

The one issue I take with the above paper, while agreeing with the conclusion, is disagreeing on the cause. The authors state the cause to be low capillary perfusion pressures, which may be a contributory factor. However, I believe the major cause of these microvascular injuries is direct damage by the Spike Protein, which the authors only speculate as a cause. 

Independent of the effect of inflammatory blood cells on the microvessels the vascular system including capillaries could be directly damaged by SARS-CoV2 virus or affected by cytokines generating an inflammatory and prothrombotic vascular wall. 

It is ever clearer that protecting and healing the Endothlieum from the Spike Protein and its damage is perhaps the most important step we can take to neutralize its effects.