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Endothelial dysfunction in ME/CFS patients (Sandvik, Mella, Fluge et al, 2023)

pattismith

Senior Member
Messages
3,932
Maybe the ACS PULS score markers should be investigated? I don't know if they are sensitive enough though

MRNA COVID vaccines dramatically increase endothelial inflammatory markers and ACS risk as measured by the PULS cardiac test: A warning | Circulation; 144(SUPPL 1), 2021. | EMBASE (bvsalud.org)

Our group has been using the PLUS Cardiac Test (GD Biosciences, Inc, Irvine, CA) a clinically validated measurement of multiple protein biomarkers which generates a score predicting the 5 yr risk (percentage chance) of a new Acute Coronary Syndrome (ACS).

The score is based on changes from the norm of multiple protein biomarkers including

-IL-16, a proinflammatory cytokine,
-soluble Fas, an inducer of apoptosis, and
-Hepatocyte Growth Factor (HGF)
which serves as a marker for chemotaxis of T-cells into epithelium and cardiac tissue, among other markers.

Elevation above the norm increases the PULS score, while decreases below the norm lowers the PULS score.

The score has been measured every 3-6 months in our patient population for 8 years. Recently, with the advent of the mRNA COVID 19 vaccines (vac) by Moderna and Pfizer, dramatic changes in the PULS score became apparent in most patients.

This report summarizes those results.
A total of 566 pts, aged 28 to 97, MF ratio 11 seen in a preventive cardiology practice had a new PULS test drawn from 2 to 10 weeks following the 2 COVID shot and was compared to the previous PULS score drawn 3 to 5 months previously pre- shot.
-Baseline IL-16 increased from 35=/-20 above the norm to 82 =/- 75 above the norm post-vac;s
-Fas increased from 22+/- 15 above the norm to 46=/-24 above the norm post-vac;
-HGF increased from 42+/-12 above the norm to 86+/-31 above the norm post-vac.

These changes resulted in an increase of the PULS score from 11% 5 yr ACS risk to 25% 5 yr ACS risk.
At the time of this report, these changes persist for at least 2.5 months post second dose of vac.

We conclude that the mRNA vacs dramatically increase inflammation on the endothelium and T cell infiltration of cardiac muscle and may account for the observations of increased thrombosis, cardiomyopathy, and other vascular events following vaccination.
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Uncover Your Risk for Heart Disease with The PULS Cardiac Test (dremina.com)
 
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Oliver3

Senior Member
Messages
846
Surely this is a connective tissue problem in the veins themselves. I keep coming back to the fact that I've never seen anyone with CFS who has good collagen.
Isn't it the collagen that allows autoimmunity to develop?
Have they isolated genes for pots etc?
I can't help thinking that crispr or sone gene editing/ stem cell therapy will be needed
 

SWAlexander

Senior Member
Messages
1,898
I keep coming back to the fact that I've never seen anyone with CFS who has good collagen.
I agree. Macular degeneration is a part of it. My left eye has two black spots. I wish Jennifer Doudna would consider looking into the collagen gene CTRP5.
 

Oliver3

Senior Member
Messages
846
I agree. Macular degeneration is a part of it. My left eye has two black spots. I wish Jennifer Doudna would consider looking into the collagen gene CTRP5.
I think Jen Brea has developed a company to look at tissue type.
I think tissue type, by how we feel is something only us sufferers understand . So researchers who are fit and healthy, come from that paradigm, looking at things through a lens that is different to our understanding of things.
I'm no good at detail but better at general intuition andI'm almost positive this is , at root cause, is collagen related.
I'm far more interested in what regenerative medicine can do. There was a time, for most of us when we were well, but our resilience wax breached far quicker than most. It's obviously not a random process when most of us have some kind of EDS traits or premature ageing.

Perhaps naviauxs hearling cycles can return us past the threshold where we got sick but personally I think if some of these genes can be altered we have a better chance.
The RCCCX theory is a brilliantly observed truth in my opinion. I've noticed people from my " tribe" all my life. It's a certain pallor, skin thickness etc etc. They all similar views on life , similar experiential ideas
I think in the future we will realise there are many different forms of collagen types and they will correspond to Jung's idea of archetypes.
I also think collagen type is about hierachy. Physichally a society needs the weak and the strong. Imagine the wars I'd we were all strong and bold.
There's a fighter in the UFC called yoel Romero. He's in his mid forties. He had a severe eye injury after a fight. The doctor who examined him phoned the management of the company and said who is this guy? He's a freak of nature. His almost detached retina was knitting back together in the e.r. dept.
If I had that kind of physichal muscle and collagen , I know I'd heal quick too. I'm mid forties. I can barely stand up!_im not muscle bound and have thick swathes of collagen all over my body.
I also think cell strength , mitochondrial strength must have some lack of strength to it.
Psychologically, I also think we are often codependent s. It's like our external boundaries are like our internal ones, weak. Again I think this is a mechanism for low resilience and subsequent social order
Why are we slow healers? Premature agers. Low muscle mass, endothelially asthmatic, autistic lite??? I think if you reverse engineer past the autoimmunity, it's just our collagen versus a poisonous world is not a good mix.

Please excuse my ramblings but I want out of this hell, like we all do and surely crispr has gotta be the best shot ultimately, or sone way to strengthen collagen and it's constituent parts.
If our very vascular system is compromised as well as our blood deformability through collagen, how do we expect to get better?

I've written to omf before about a researcher called Liz Parrish who is experimenting on herself with telemore relengthening and other ideas to regrow tissue and reverse ageing.bi feel this avenue should be at least looked at.
I've seen also that that a veds med is in stage three trials, and it's. Changing how collagen is expressed. It's not gene editing or anything but just proves to me that we are all on a collage expression spectrum and our end is not the good end.

Please forgive my generalisation.like I say, I think I'm quite good aaat general ideas and this has been sitting in my head but I can't back any of it up! Any scientists who can?
 

Murph

:)
Messages
1,799
I'm no good at detail but better at general intuition andI'm almost positive this is , at root cause, is collagen related.
There's a good scientific basis here: collagen and connective tissue probelms are a plausible candidate for being causal in this disease.

But I also see evidence of what happens when a person dwells on an idea too long: it starts to move to the centre of your thinking, and you create theories that the whole of society depends on this one idea.

I've noticed people from my " tribe" all my life. It's a certain pallor, skin thickness etc etc. They all similar views on life , similar experiential ideas
I think in the future we will realise there are many different forms of collagen types and they will correspond to Jung's idea of archetypes.
I also think collagen type is about hierachy. Physichally a society needs the weak and the strong. Imagine the wars I'd we were all strong and bold.

When you follow the science, one of the hardest things to do is be nimble. Follow the facts, admit multiple possibilities, change your mind when data comes in. It's probably actually not even possible - even scientists themselves, who pay great lip service to this idea, in fact follow their pet theories to the grave.

Collagen is a possible theory for explaining mecfs. but it's not the only one and it needn't be central to the disease. Worth looking at but worth remaining open to lots of other ideas too. What's more, the cause is likely to be the convergence of multiple things.

As an example, everyone who gets MS had an EBV infection. But not everyone who got EBV has MS. EBV is causal. But not the only cause. It's like oxygen is to fire: you need oxygen for fire, but people don't generally say that oxygen causes fires, we focus more on fuel and even more on sparks. Collagen problems could relate to mecfs like oxygen relates to fires.
 

Oliver3

Senior Member
Messages
846
I understand and am not hyperfocused to the point I think I'm right.
There are gonna be different tributaries to this disease expression.
I actually don't want to be right about collagen being a root cause as it's harder to treat than day autoimmunity. It's literally the building blocks we are made from. If it's that, well it's gonna be a hard fix.
I guess what I was trying to say is that science seems to extrapolate from their own biases of well being.
All the parameters that are set as healthy for normies don't seem to be correct parameters for us.
Most people with down syndrome have a space between their big toe and next time but you can have that same configuration and be completely normal . I get totally your emphasis on being nimble scientifically and intellectually.
My worry is, that the collagen thing is not taken seriously by most. It just seems like a paradigm that's not being opened properly to observe in an open minded way.
You know, I've looked at loads of theories in my non science mind, like autoimmunity, ebv, mental illness, blood viscosity, b vitamins like we all have.
It just seems I always come back to the point that we all have an allostatic breaking point.
I imagine even the most collagen rich, non hypermobile , beast of a person could have m.e. induced under extreme conditions.
It's just that we father quickly. We are the canaries in the coal mine. Naviauxs cell danger response seems to be kicked off in us easily...why? I can't help but always come back to collagen and tissue type
 
Messages
53
So I've been reading stuff lately and came up with this theory in my head. Probably too naïve and far fetched, but here it goes anyway :)

Maureen Hanson's group found 'dysfunctional' monocytes being the biggest difference between CFS and controls in their 2022 single-cell transcriptomics study. These monocytes were primed to enter tissues but they were still in circulation. Were they stuck and couldn't reach sites of infection?

Monocytes are attracted to sites of infection via chemical messengers and then penetrate blood vessel walls through a process called extravasation. This is a complex, multi-step process that involves at least 20 different receptors, cytokines, chemokines, etc. A problem in any of those may in theory prevent monocytes from exiting blood vessels. Extravasation also requires changes in physical blood flow parameters--the flow needs to slow down, which normally happens as a result of vasodilation. If vasodilation doesn't happen monocytes can't exit blood vessels. If endothelial dysfunction is present like this study found, wouldn't that impair monocyte extravasation?

Once monocytes penetrate tissues, they differentiate into macrophages and dendritic cells. Those cells are important part of immune response in tissues. Macrophages are responsible to gobbling up infected cells and cleaning up debris. Dendritic cells sample pathogens and then present antigens to other cells so that antibodies can be produced. If these two guys don't show up to the fight, what will happen? Are we going to end up with a smoldering infection?

If we have a smoldering but active infection somewhere in tissues (could be the gut for example), wouldn't that warrant the kind of local innate immune activation that Robert Phair is talking about, with it's IFNa feedback loop, itaconate shunt and all the symptoms that follow?
 

SWAlexander

Senior Member
Messages
1,898
There is more involved in Collagen - muscle weakness.

Here are some of my random incomplete notes on the subject. I was "diagnosed" with Post Polio syndrome (PPS).
The reason I´m not 100% convinced about having PPS is, that I know since 2010 my DNA shows the onset of Macular degeneration (COL6A3 genes) which is Collagen related. My search for answers continues, though it looks like a never-ending story.

Collagen could be related to an intergenic region a stretch of DNA sequences located between genes. Intergenic regions are the stretches of DNA located between genes. In humans, intergenic regions are non-protein-coding and comprise a large majority. If this is the case crispr cas9 could not be (yet) effective.

Collagen vascular diseases are autoimmune diseases that occur when the body's immune system attacks its own skin, tissues and organs.

Collagen could also be related to Bethlem myopathy. This rare disease is affecting the skeletal muscles and connective tissue affecting the skeletal muscles and connective tissue. The disease is characterized by slowly progressive muscle weakness and joint stiffness (contractures). It most often affects the fingers, wrists, elbows, and ankles. Bethlem myopathy is an early-onset benign autosomal dominant myopathy with contractures caused by mutations in collagen type VI genes. It has been reported that onset occurs in early childhood. It is caused by genetic changes (changes) in the COL6A1, COL6A2, or COL6A3 genes. Most cases are inherited in an autosomal dominant manner, but in rare cases the disease is autosomal recessive. There is no cure for myopathy itself. However, it can be treated to improve symptoms.

This is a very good part: If myopathy is related to an illness, like a virus or electrolyte imbalance, the muscle symptoms will improve when the underlying condition resolves. Immunosuppressants can help relieve symptoms of certain types of myopathy.
1676269168328.png
 
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SWAlexander

Senior Member
Messages
1,898
Extravasation also requires changes in physical blood flow parameters--the flow needs to slow down, which normally happens as a result of vasodilation. If vasodilation doesn't happen monocytes can't exit blood vessels. If endothelial dysfunction is present like this study found, wouldn't that impair monocyte extravasation?

Very interesting and worth following.

Dendritic cells sample pathogens and then present antigens to other cells so that antibodies can be produced. If these two guys don't show up to the fight, what will happen? Are we going to end up with a smoldering infection?
This is my thought too since viruses like (HHV6 etc) and bacteria can linger and be reawakened.
 

Wishful

Senior Member
Messages
5,684
Location
Alberta
There's a good scientific basis here: collagen and connective tissue probelms are a plausible candidate for being causal in this disease.

I disagree. That hypothesis fails my ME test because it doesn't fit how rapidly I switched from full ME to full non-ME (temporary remissions), via several chemicals that seem unlikely to quickly/directly affect collagen. I also lack any noticeable collagen problems. ME might cause collagen problems in some people, but I rate it very low as a root cause.
 

Oliver3

Senior Member
Messages
846
Well that's sounds autoimmune. Which is a direct result of collagen weakness, lack of integrity in the stomach.
This is the thing. It doesn't necessarily have to be a systemic problem with collagen.
Viruses invade collagen that is not strong etc etc.
Anyway, I get it,we are all going off our own experience.
But Ive net so many people with EDS who could be described as having CFS and vice verse.
That's too much of a coincidence to me.
Ron has EDS so does Whitney and his sister.
I hope you're right and it's very fixable and soon.
Surely if phairs hypothesis works we might see some well known sufferes getting better
 

GreenEdge

Senior Member
Messages
565
Location
Brisbane, Australia
Could the cause of Endothelial dysfunction be insulin resistance? :xeyes:

To commercialize a disease drug companies :devil: will obfuscate the cause and sell you drugs to suppress symptoms.
Big pharma know that treating only symptoms guarantees continuous sales well into the future.

If you were informed (of the cause), wouldn't you just change your behavior and cure yourself (for free). :nerd:

I think this video @ 5:00 describes what's happening.
 

junkcrap50

Senior Member
Messages
1,330
In Germany they are testing a drug called Vericiguat from Merck. Which should dilate blood vessels. It is already FDA apporoved. Maybe this help these subgroups.
@Dude @lenora @pattismith There is also calcium dobesilate (Doxium). It is a vasoprotective drug used in endothelial disorders ( e.g. diabetic retinopathy, chronic venous disease and hemorrhoidal disease) with states of fragility and altered capillary permiability with effects on correcting capillary permeability, platelet aggregation and blood viscosity. It is not approved in the US but available in the rest of the world, Europe Asia, Latin America, etc.
 

GreenEdge

Senior Member
Messages
565
Location
Brisbane, Australia
Drugs to dilate blood vessels? I hope it's only temporary. Dilate and then contract - both states are important.

Why pay for an expensive drug with potential side effects when a far safer option vitamin B3 (Niacin) already exists and has a long safety record of over 50 years, see my post here.