1/ 🚨🧵
RAPID AAD-Aortic Aneurysm and Dissection (tearing/rupture) is lethal.
Plasmid DNA is dsDNA.
dsDNA can enter cells from the body's own sources, or a contamination event (💉)
dsDNA is shown to cause AAD via the STING path.
A thread on a study, and adverse event cases.
2/ The study:
Critical Role of Cytosolic DNA and Its Sensing Adaptor STING in Aortic Degeneration, Dissection, and Rupture
. 2020;141:42–66
doi.org/10.1161/CIRCUL…
ahajournals.org/doi/10.1161/CI…
3/ AAD is an extremely lethal cardiovascular event.
The STING pathway is implicated in tissue destruction and inflammation in numerous conditions and diseases.
The study done in vivo, saw the presence of dsDNA, and tracked STING activation in animal/human models in AAD.
4/ Specifically, cytosolic (outside of nucleus, but still in the cell) DNA and STING pathway activation occurred, in combination with macrophages.
The presence of cytosolic DNA in aortic tissues from patients with sporadic ascending thoracic AAD, showed immune system activation,
5/ as a response to dsDNA that should not be there. In patients w/ AAD, cytosolic dsDNA and STING pathway activation were detected in specific cell types, like smooth muscle cells in aortic tissues.
Smooth muscle cells impact the structural integrity of the aortic wall.
6/ Order of operations:
Presence of exogenous dsDNA in aortic tissues, from sources such as damaged nuclei, mitochondria (or 🧬💉contamination?) is recognized by cellular "sensors" called the STING pathway. The STING pathway then activates the immune system as a response to the
7/ presence of genetic material that should not be floating around in the cytoplasm. This can occur all over the body, but right now we are focusing on rapid onset lethal aortic dissection. Immune system activation leads to the presence of interferons and macrophages.
8/ because the STING pathway is activated, a rapid inflammatory response and condition occurs, and in this case, it is happening in the heart, in the aorta. Macrophages are "activated" and rush to the area.
This starts a cascade of really bad stuff. The smooth muscle cells
9/ inside the wall of the aorta in the heart, then release THEIR OWN dsDNA as a response to being inflamed. This is a direct result of inflammation and damage being done by the immune attack on the body's own aorta and heart.
Macrophages then "engulf" the dsDNA that is
10/ getting kicked out of the smooth muscle cells, which is different dsDNA than the dsDNA which kicked off this whole domino effect.
Then subsequent activation of STING pathway in macrophages contributes to downstream effects, including MMP-9 production and extracellular matrix
11/ (ECM) degradation.
Note: MMP-9 is an enzyme that plays a role in the degradation of extracellular matrix (ECM), which is a part of tissues that provides structural support.
The production of MMP-9 by macrophages contributes to the degradation of the ECM, thus remodeling and
12/ dissection of the aorta. This sequence drives AAD.
This includes smooth muscle cell (SMC) injury, inflammation, and ECM degradation--causing a lethal situation.
13/ just to be clear, the initial activation of STING before smooth muscle cell involvement with that area releasing it's OWN dsDNA are two separate parts of the domino of events, the cascade that kicks off this entire mechanisms. It can and does occur in people without
14/ an external dna contamination event.
However, exogenous dsDNA entering cells in the heart, should plausibly activate this same pathway.
In order for the heart, and the cardiomyocyte to be "transfected", a lipid nanoparticle would have to have a molar ratio of 10:1, that is
15/ 10:1 ratio of ionizable lipids to dsDNA plasmid contamination combined with modRNA to enter the area of that heart, especially the cardiomyocyte.
"Ionizable Lipid Nanoparticle-Mediated Delivery of Plasmid DNA in Cardiomyocytes"
dovepress.com/ionizable-lipi…
16/ a concern would be, if this occurred after vaccination, and if an LNP was loaded with dsDNA and made its way to the heart, the cardiomyocyte, and namely, the aorta.
17/ An autopsy case report of aortic dissection after mRNA COVID-19 vaccination: correspondence
Leg Med (Tokyo). 2023 Feb; 60: 102169.
Published online 2022 Oct 26. doi: 10.1016/j.legalmed.2022.102169 ncbi.nlm.nih.gov/pmc/articles/P…
18/ An autopsy case report of aortic dissection complicated with histiolymphocytic pericarditis and aortic inflammation after mRNA COVID-19 vaccination
DOI: 10.1016/j.legalmed.2022.102154
pubmed.ncbi.nlm.nih.gov/36191411/
19/ Myopericarditis and Acute Aortic Dissection after Receiving mRNA Based COVID 19 Vaccine: Cases Report and Literature Reviewed - รายงานผู้ป่วยที่เกิดกล้ามเนื้อหัวใจอักเสบและ ผนังหลอดเลือดแดงใหญ่ปริภายหลังได้รับ mRNA based COVID-19 วัคซีน และการทบทวนวารสารฯ
21/ “Spontaneous” Coronary Artery Dissection After SARS-CoV-2 Messenger RNA Vaccination
DOI: jscai.org/article/S2772-…
doi.org/10.1016/j.jsca…
22/ Could the spike expression be involved too? Sure
Got nucleocapsid?
@P_J_Buckhaults
@DrJBhattacharya
@drdrew
@SenatorRennick
23/ **** note: "Plasmid DNA is dsDNA" refers to the DNA contamination event that everyone is currently speaking to right now. This is speaking to the biotech plasmid that contains the SV40 promoter, the antibiotic resistance, the gene encoding for spike, etc.
@P_J_Buckhaults
Chain reaction
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