SARS-COV-2 elevated DNA damage risk in cardiomyocytes without direct infection
"Shocking if true".
Granted I didn’t search that far and wide, but I didn’t see many people mentioning this fairly enlighting paper anywhere.
SARS-COV-2 to induce cell stress and elevated DNA damage risk in cardiomyocytes without direct infection
Background: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in 2020 has led to millions of deaths worldwide. Case reports suggested that infection of SARS-CoV-2 is potentially associated with occurrences of cardiovascular pathology. However, the mode of action and mechanisms of SARS-CoV-2 influencing cardiomyocytes still remain largely unclear.
Aims: To explore the mechanisms underlying cardiomyocytes damage induced by SARS-CoV-2 infection.
Materials & Methods: the serum markers of cardiovascular injury were analyzed by ELISA. The isolated SARS-CoV-2 virus were co-cultured with human cardiomyocytes (AC16) and immunofluorescence assay was used evaluate the invasion of virus. Moreover, serum obtained from acute stage of SARS-CoV-2 infected patients and healthy controls were used to incubate with AC16 cells, then indicators associated with cell stress and DNA damage were analyzed by Western-blot.
Results: we found that high-sensitivity troponin T (hsTnT), an indicator of cardiovascular disease, was higher in the acute stage of COVID-19. Additionally, in vitro coculture of SARS-CoV-2 and AC16 cells showed almost no infectious ability of SARS-CoV-2 to directly infect AC16 cells. Results of serum treatment suggested that serum from infected subjects induced cell stress (upregulation of p53 and HSP70) and elevation of DNA damage risk (increased γH2Ax and H3K79me2) in AC16.
Discussion: our observations indicated a hard way for SARS-CoV-2 to infect cardiomyocytes directly. However, infection-induced immune storm in serum could bring stress and elevated DNA damage risks to cardiovascular system.
Conclusion: These findings indicated the possibilities of SARS-CoV-2 inducing stress and elevating DNA damage risk to cardiomyocytes without direct infection.
Now, this is quite an interesting paper, in line with a paper I find fairly important and many somewhat ignored. The one inside the article below.
(That paper was retracted, and usually, these are the ones I pay 100x attention to, now, does anyone care to guess WHY it was retracted ? And people wonder why 99% of papers with contradictory findings end their discussion sections with TAKE THE VACCINES BRO)
Authors propose it is too hard for SARS-CoV-2 to directly infect the cells that are responsible for contracting the muscle in your heart (the main job of the cardiomyocytes), and the damage we are seeing from the viral infection is inflicted via other mechanisms, and they tested their hypothesis in vitro, which usually it is far easier for a virus to infect a cell.
But they found that all the immunity weirdness (cytokine storm) going on was inducing DNA damage risk to cardiomyocytes.
One of the consequences of inflammatory burdens in SARS-CoV-2-induced acute respiratory disease is the so-called “cytokine storm”; excessive pro-inflammatory cytokines were produced and released into the circulation of blood leading to multiorgan failure and even death.9, 10 Furthermore, the inflammatory cytokines could induce DNA damage and even inhibition of associated DNA repair.11 Another research reported that both cardiomyocytes, vascular endothelium, cardiac fibroblasts, pericytes, and vascular smooth cells express angiotensin-converting enzyme 2 (ACE2) at respective levels.12, 13 However, whether SARS-CoV-2 directly proliferates in the cardiomyocytes is still under debate.
Inability to infect human cardiomyocytes of SARS-COV-2 virus
To further study the way of SARS-COV-2 induces cardiac stress, the human cardiomyocyte cells (AC16) were used for the host cell infection analysis. The AC16 cells were incubated with isolated SARS-COV-2, and then the positive serum was used to probe the virus inside the cells. Strong fluorescent signals could be observed in Vero cells while hardly can be seen in AC16 cells after incubation with the SARS-COV-2 virus. The observation indicated that SARS-COV-2 merely directly infects cardiomyocytes. To further evaluate the possible cause of the inability of SARS-COV-2 to penetrate the cell membrane of AC16, we analyzed levels of two known receptors (ACE2 and TMPRSS, which were required by SARS-COV-2 to invade cells) in different cell types. The results suggested that compared with lung or bronchial cells, ACE2 and TMPRSS were both at a relatively low level in AC16 cells
Under the parameters of this research, SARS-CoV-2 could not penetrate quite well the cell membrane they used, and both the main receptors SARS-CoV-2 mainly uses are relatively low in these cells.
I would like to note that SARS-CoV-2 uses a lot of other receptors to hijack cells, but when using different receptors, it will often end up in cell death and inflammation of the region, so while the virus might not be directly infecting these cells, it can be doing heart damage in some people via other mechanisms.
Serum from subjects in an acute stage induces upregulation of DNA damage and cell stress markers in AC16 cells
After infection, AC16 cells were collected, and the cell stress markers, such as p53 and HSP70, were evaluated. The results suggested that the levels of stress signal proteins, such as p53 and HSP70, were significantly elevated due to the treatment of serum with SARS-COV-2 infection compared to negative controls. Nonetheless, DNA damage is another critical biological event; we further analyzed the markers of DNA damage response. Relative levels of γH2Ax and H3K79me2 were also found upregulated in AC16 cells, which indicates that the incidence of DNA damage events increased under the treatment of serum from SARS-COV-2 infection.
In line with the paper in my article at the start of this one, they found high levels of specific proteins and markers specific to DNA damage (γH2Ax and H3K79me2). γH2Ax is a known molecular marker for DNA damage. Here is a good paper on this subject. Full paper by alternative means here.
The most important part for the future when it comes to this virus, in my opinion.
The closing arguments of the paper being discussed in this article.
Given what we covered so far in this Substack, I think the answer to this question is somewhat clear, at least at some levels. Many of the disease effects are derived from the Spike Protein, driven by a systemic bystander effect, in a state where your body is severely depleted from the necessary nutrients to repair itself, and flooded with enough inflammatory proteins it takes a toll in moderate to severe cases.
The ROS aspect is among the most important ones in regards to all this, because of the mitochondrial aspect of it all. One example of many you can find in under a minute.
Using different receptors sets off a myriad of types of cell deaths in all types of cells, continuously driving inflammation and ROS upwards, depleting your body from the necessary resources. A lot of my recent articles about the virus are all converging into the same place, by sheer coincidence (merely following the evidence and not jumping to conclusions).
For the longest time I thought, perhaps my superficial observation based on conversations with very smart doctor-friends was just that, superficial. Guess not.
You can find more and understand the significance of mitochondria in the article below, among many others.
Perhaps the friend with who I researched the Reverse AIDS hypothesis together was correct, we both were. Me with my bioenergy observation, and him with the assertion that the Spike Protein is messing with one single gene, and the entire cascade is born from that interaction.
For the last few weeks I have been giving time for people to absorb the information, but I might have to pick up the pace for the things I have in mind, and just keep referring back when needed. An FYI of some sort.
I wish all my readers I nice and productive week.
PS: A reader asked me weeks ago to write about Ferroptosis, perhaps I will do a series of posts solely based on that. It is my favorite form of cell death. So elegant and intricated.
Deep appreciation for all the supporters!
I think a number of posts on Ferroptosis would be excellent, considering the relatively recent discovery of this mechanism of cellular death.
https://jhoonline.biomedcentral.com/track/pdf/10.1186/s13045-019-0720-y.pdf
"Ferroptosis is programmed necrosis mainly triggered by extra-mitochondrial lipid peroxidation arising from an iron-dependent ROS accretion. Excessive iron originally from aberrant iron metabolism or maladjustment of two major redox systems (lipid peroxidation and thiols) was the main incentive factors of ROS production. "
"Interestingly, microRNA and long non-coding RNA (lncRNA) are increasingly recognized as the crucial mediators in the regulation of ferroptosis."
Well there is that RNA again!
Do you have the impression that this is something that can be bio-"weaponized" or not?
Asking for some friends.
Thank you! 😊💕