I used to think that fibrosis was permanent and irreversible, until I was corrected by a cardiologist. If you leave it too long then it can be due to remodelling, but there are some drugs that, if given early, can mitigate some of the damage or inhibit the process:
Novel Therapies for the Treatment of Cardiac Fibrosis Following Myocardial Infarction (2022)
"4.4.1. ReninâAngiotensinâAldosterone System (RAAS) Inhibitors RAAS inhibitors are widely used to target cardiac fibrosis. Drugs such as lisinopril, losartan, amlodipine, and spironolactone have proven their anti-fibrotic effect on cardiomyocytes [23,99,100]. A recent study demonstrated that a new first-in-class angiotensin receptor inhibitor, sacubitril/valsartan, can suppress the effect of RAAS during cardiac remodeling by blocking angiotensin II type 1 receptors and activating vasoactive peptides through the inhibition of the neprilysin enzyme, which is responsible for their degradation [101]. Sacubitril/valsartan prevented maladaptive cardiac fibrosis and dysfunction by blocking cardiac fibroblast activation and proliferation in a mouse model of pressure overloadâinduced hypertrophy [102]."
MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models.
I wonder if these work not just on the liver but on other tissue prone to fibrosis?
Melatonin safeguards against fatty liver by antagonizing TRAFs-mediated ASK1 deubiquitination and stabilization in a β-arrestin-1 dependent manner
"...Melatonin treatment significantly suppressed the ASK1 upregulation and the phosphorylation of ASK1, MKK3/6, MKK4/7, p38, and JNK."
"...Although melatonin administration did not alter food intake, it significantly alleviated fatty liver phenotypes, including the body weight gain, insulin resistance, hepatic lipid accumulation, steatohepatitis, and fibrosis in a high-fat diet (HFD)-induced NAFLD mouse model (in vivo)."
It would be remiss of me not to bring magnesium into the discussion:
Magnesium enhances cardiomyocyte proliferation and suppresses cardiac fibrosis induced by chronic ACTH exposure in rats
Jelena PetroviÄ et al. Magnes Res. 2021.
"...Our results show, for the first time, that administration of Mg in rats was effective in ameliorating the development of ACTH-evoked cardiac fibrosis, while facilitating cardiomyocyte proliferation. Furthermore, we propose that Mg supplementation attenuates ACTH-induced HPA axis hyperactivity, as one of the underlying plausible mechanisms, which may contribute to its cardioprotective effects."
I'm writing that up currently. Chelated Mg has higher bioavailability with less laxative effects. My personal favourite is chelated with glycine, glycinate. Threonate is great for crossing the blood-brain barrier.
Two points I keep making about the myocarditis issue:
(1) it is likely that myocarditis is just the most visible and easily diagnosable manifestation of a process which - given what we know about distribution - is happening throughout the body.
(2) there is no reason to believe that cases which never required healthcare intervention (it is self-limiting in most cases, and complaining about side effects was most definitely NOT encouraged) are not at some risk as well. So we could be dealing with an even more massive problem than thought.
Notably, autopsies are finding microinflammation in the heart of people who died suddenly, after no diagnosis during life:
đŻ Agreed. On both counts. Effects are systemic and no tissue is left untouched by either LNPs, exosomes or free Spike, as well as bystander effects and persistent expression.
I will be reviewing effects on organ stem cells in future too.
Just wondering if you ever saw this piece (I wrote it):
It makes a case for early and apparently resolving PAH to be quite common based on anatomical principles - ie the lungs take a particularly big hit after these products are injected.
But what if there was also previously undiagnosed PFO, which are said to be present (in various sizes) in up to 25% of people, usually quite harmlessly.
In the presence of a PFO, surely small but possibly significant quantities of vaccinal product would - by being shunted from the right atrium into the left atrium - end up avoiding the lungs, entering the coronary circulation beforehand.
This could dramatically increase the amount of transfection taking place in the myocardial tissue.
Systemic thromboemboli in patients with Covid-19 may result from paradoxical embolization
"...Patients with COVID-19 pneumonia will almost certainly have some intra-pulmonary shunt [[10], [11], [12]]. Previous studies have reported that the prevalence of intra-pulmonary shunt is higher in patients with cryptogenic stroke (22%) than in matched controls (10%) [13]. This suggests that intra-pulmonary shunt could facilitate ischaemic cerebrovascular events [13]."
"...The prevalence of patent foramen ovale (PFO) in the general population is high (20â30%) but is even higher in patients who have a stroke (50%). Thus, the striking absence of data on patients with PFO who develop COVID-19 suggests that this is being under-diagnosed."
We have had almost a ban on autopsies since 2020, but also in my experience in Canada for the past twenty years.
"We know enough from our CT scans and lab work, etc., that we do not need to undertake expensive PM's."
I have not looked closely at the reported autopsy series since 2021 which have implicated the vaxx spikes in about 75% of the deaths; most of the attention was on tissue and cellular level markers and I didn't note reports on cardiac structure. Existence of PFO would almost automatically have deflected any search for another cause of SADS, popular since 2021.
My younger sister had PAH; I assumed that it was due to pulmonary microthrombi from the spike:ACE2 interaction, or possibly the PF4 feature. I thought that the PAH was a consequence of RVH and mitral valve incompetence. Of course my suggestion was rapidly rejected, with the predictable outcome.
Right. My elder sister had the aortitis, dissected, and has survived the surgery. The intensivist was not in the least interested in any discussion of vaxx injury.
Eugh: "...Whatâs more, angiotensin II (Ang II)-induced STING could be accelerated by ER stress activator, while being markedly abolished by the ER stress inhibitor. We then found that whether co-treated with or without transforming growth factor-beta 1 (TGF-β1), cardiac fibroblasts cultured in the conditional medium (CM) from Ang II-incubated cardiomyocytes with STING knockdown exhibited significantly reduced fibrosis, as displayed by the clearly down-regulated expression of Îą-SMA, Collagen type I (Col I) and Collagen type III (Col III). "
I used to think that fibrosis was permanent and irreversible, until I was corrected by a cardiologist. If you leave it too long then it can be due to remodelling, but there are some drugs that, if given early, can mitigate some of the damage or inhibit the process:
Novel Therapies for the Treatment of Cardiac Fibrosis Following Myocardial Infarction (2022)
"4.4.1. ReninâAngiotensinâAldosterone System (RAAS) Inhibitors RAAS inhibitors are widely used to target cardiac fibrosis. Drugs such as lisinopril, losartan, amlodipine, and spironolactone have proven their anti-fibrotic effect on cardiomyocytes [23,99,100]. A recent study demonstrated that a new first-in-class angiotensin receptor inhibitor, sacubitril/valsartan, can suppress the effect of RAAS during cardiac remodeling by blocking angiotensin II type 1 receptors and activating vasoactive peptides through the inhibition of the neprilysin enzyme, which is responsible for their degradation [101]. Sacubitril/valsartan prevented maladaptive cardiac fibrosis and dysfunction by blocking cardiac fibroblast activation and proliferation in a mouse model of pressure overloadâinduced hypertrophy [102]."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496565/
"First-in-class MKK4 inhibitors enhance liver regeneration and prevent liver failure" https://www.cell.com/cell/fulltext/S0092-8674(24)00225-3
MKK4i increased liver regeneration upon hepatectomy in murine and porcine models, allowed for survival of pigs in a lethal 85% hepatectomy model, and showed antisteatotic and antifibrotic effects in liver disease mouse models.
I wonder if these work not just on the liver but on other tissue prone to fibrosis?
Yes, it would appear so:
Mkk4 Is a Negative Regulator of the Transforming Growth Factor Beta 1 Signaling Associated With Atrial Remodeling and Arrhythmogenesis With Age
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187508/
An off-the-shelf solution, melatonin is also very useful after MI, also targeting mkk4 as well as 7:
Effect of Melatonin on Cardiac Injury after Primary Percutaneous Coronary Intervention: a Randomized Controlled Trial
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4518113
Melatonin safeguards against fatty liver by antagonizing TRAFs-mediated ASK1 deubiquitination and stabilization in a β-arrestin-1 dependent manner
"...Melatonin treatment significantly suppressed the ASK1 upregulation and the phosphorylation of ASK1, MKK3/6, MKK4/7, p38, and JNK."
"...Although melatonin administration did not alter food intake, it significantly alleviated fatty liver phenotypes, including the body weight gain, insulin resistance, hepatic lipid accumulation, steatohepatitis, and fibrosis in a high-fat diet (HFD)-induced NAFLD mouse model (in vivo)."
https://pubmed.ncbi.nlm.nih.gov/31541591/
It would be remiss of me not to bring magnesium into the discussion:
Magnesium enhances cardiomyocyte proliferation and suppresses cardiac fibrosis induced by chronic ACTH exposure in rats
Jelena PetroviÄ et al. Magnes Res. 2021.
"...Our results show, for the first time, that administration of Mg in rats was effective in ameliorating the development of ACTH-evoked cardiac fibrosis, while facilitating cardiomyocyte proliferation. Furthermore, we propose that Mg supplementation attenuates ACTH-induced HPA axis hyperactivity, as one of the underlying plausible mechanisms, which may contribute to its cardioprotective effects."
https://pubmed.ncbi.nlm.nih.gov/34463274/
Excellent
Cyprinus carpio - not good but an excellent and thorough examination. Your standard is the pinnacle others hope to acheive. Happy Easter.
Thank you NatteringNaybob. And Happy Easter to you too!
Any idea which type of magnesium to take?
C-VAM only called that if damage occurs within 14 days of vax. But you aren't considered vaxxed until after 28 days. Clever/ diabolical!
I'm writing that up currently. Chelated Mg has higher bioavailability with less laxative effects. My personal favourite is chelated with glycine, glycinate. Threonate is great for crossing the blood-brain barrier.
would it be worth taking with GlyNAC instead of just glycine?
Magnesium glycinate for both.
Thank you for such a comprehensive piece.
Two points I keep making about the myocarditis issue:
(1) it is likely that myocarditis is just the most visible and easily diagnosable manifestation of a process which - given what we know about distribution - is happening throughout the body.
(2) there is no reason to believe that cases which never required healthcare intervention (it is self-limiting in most cases, and complaining about side effects was most definitely NOT encouraged) are not at some risk as well. So we could be dealing with an even more massive problem than thought.
Notably, autopsies are finding microinflammation in the heart of people who died suddenly, after no diagnosis during life:
https://hartuk.substack.com/p/new-autopsy-evidence-from-japan-myocarditis
đŻ Agreed. On both counts. Effects are systemic and no tissue is left untouched by either LNPs, exosomes or free Spike, as well as bystander effects and persistent expression.
I will be reviewing effects on organ stem cells in future too.
A theory:
Just wondering if you ever saw this piece (I wrote it):
It makes a case for early and apparently resolving PAH to be quite common based on anatomical principles - ie the lungs take a particularly big hit after these products are injected.
But what if there was also previously undiagnosed PFO, which are said to be present (in various sizes) in up to 25% of people, usually quite harmlessly.
In the presence of a PFO, surely small but possibly significant quantities of vaccinal product would - by being shunted from the right atrium into the left atrium - end up avoiding the lungs, entering the coronary circulation beforehand.
This could dramatically increase the amount of transfection taking place in the myocardial tissue.
https://hartuk.substack.com/p/pah
Systemic thromboemboli in patients with Covid-19 may result from paradoxical embolization
"...Patients with COVID-19 pneumonia will almost certainly have some intra-pulmonary shunt [[10], [11], [12]]. Previous studies have reported that the prevalence of intra-pulmonary shunt is higher in patients with cryptogenic stroke (22%) than in matched controls (10%) [13]. This suggests that intra-pulmonary shunt could facilitate ischaemic cerebrovascular events [13]."
"...The prevalence of patent foramen ovale (PFO) in the general population is high (20â30%) but is even higher in patients who have a stroke (50%). Thus, the striking absence of data on patients with PFO who develop COVID-19 suggests that this is being under-diagnosed."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462541/#bb0050
Thanks for the link, no I hadn't seen it but share your concerns about PAH and future heart failure...
They don't like gathering or publishing clinical data, but if we have excess data for cases with PFO then we can look for a signal.
We have had almost a ban on autopsies since 2020, but also in my experience in Canada for the past twenty years.
"We know enough from our CT scans and lab work, etc., that we do not need to undertake expensive PM's."
I have not looked closely at the reported autopsy series since 2021 which have implicated the vaxx spikes in about 75% of the deaths; most of the attention was on tissue and cellular level markers and I didn't note reports on cardiac structure. Existence of PFO would almost automatically have deflected any search for another cause of SADS, popular since 2021.
My younger sister had PAH; I assumed that it was due to pulmonary microthrombi from the spike:ACE2 interaction, or possibly the PF4 feature. I thought that the PAH was a consequence of RVH and mitral valve incompetence. Of course my suggestion was rapidly rejected, with the predictable outcome.
Thanks. Right ventricular hypertrophy, that's directly linked to some cases of myocarditis, which all fits the pathology.
Btw I'm writing about igG4 and aortitis, after it was brought to my attention.
Right. My elder sister had the aortitis, dissected, and has survived the surgery. The intensivist was not in the least interested in any discussion of vaxx injury.
;)
https://www.sciencedirect.com/science/article/pii/S0753332220302134
Thank you Christie!
Eugh: "...Whatâs more, angiotensin II (Ang II)-induced STING could be accelerated by ER stress activator, while being markedly abolished by the ER stress inhibitor. We then found that whether co-treated with or without transforming growth factor-beta 1 (TGF-β1), cardiac fibroblasts cultured in the conditional medium (CM) from Ang II-incubated cardiomyocytes with STING knockdown exhibited significantly reduced fibrosis, as displayed by the clearly down-regulated expression of Îą-SMA, Collagen type I (Col I) and Collagen type III (Col III). "
Hiya Carp!
That's a whole lotta science for a Saturday. ;)
ânot final peer-reviewed papers (which unfortunately doesnât mean what it should)â
Multiple heavy sighs: so sad but true
Yep.