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Cardiac mast cells: the centrepiece in adverse myocardial remodelling

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002871/

Abstract
Increased numbers of mast cells have been reported in explanted human hearts with dilated cardiomyopathy and in animal models of experimentally induced hypertension, myocardial infarction, and chronic volume overload secondary to aortocaval fistula and mitral regurgitation. Accordingly, mast cells have been implicated to have a major role in the pathophysiology of these cardiovascular disorders. In vitro studies have verified that mast cell proteases are capable of activating collagenase, gelatinases and stromelysin. Recent results have shown that with chronic ventricular volume overload, there is an elevation in mast cell density, which is associated with a concomitant increase in matrix metalloproteinase (MMP) activity and extracellular matrix degradation. However, the role of the cardiac mast cell is not one dimensional, with evidence from hypertension and cardiac transplantation studies suggesting that they can also assume a pro-fibrotic phenotype in the heart. These adverse events do not occur in mast cell deficient rodents or when cardiac mast cells are pharmacologically prevented from degranulating. This review is focused on the regulation and dual roles of cardiac mast cells in: (i) activating MMPs and causing myocardial fibrillar collagen degradation and (ii) causing fibrosis in the stressed, injured or diseased heart. Moreover, there is strong evidence that premenopausal female cardioprotection may at least partly be due to gender differences in cardiac mast cells. This too will be addressed.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
@Countrygirl

10. Gender differences in cardiac mast cells
The prevalence and severity of gender differences in cardiovascular disease has been convincingly identified in human clinical studies,96 however, the underlying mechanisms responsible for the lower incidence of cardiac disease in premenopausal females are poorly understood. Since cardiac mast cells play a central role in mediating the remodelling process through the activation of MMPs leading to the subsequent degradation of the ECM, gender differences in cardiac mast cell activation and function may provide a mechanism for the cardioprotection afforded to pre-menopausal females. However, information regarding gender differences is extremely limited..

Which might also relate to the gender difference in CFS.
.
 

Countrygirl

Senior Member
Messages
5,429
Location
UK
Bad insomnia. Plus tendons are affected (sometimes very badly) --- probably from chymase secreted by Mast Cells

I have just noticed the above in your signature. For many years, my tendons have easily torn and now I have tenosynovitis and De Quervains (both thumbs) in my hands. Is this connected?

Tryptase from MCs is also most likely involved in attacking joints

This has really puzzled me as I have been bed/sofa/house bound for most of the last 35 years so wear-and-tear cannot explain my sudden wide spread arthritis, including hips, knees, spine and hands. Are you then saying that this could be a result of a mast cell disorder?

And it explains the malignant hypertension?

What about fibrosis of the skin? (very rare, but I have it and, believe me, if ME is horrid, this is worse.)

I think I need to study mast cell disorders.:(
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
@Countrygirl

Yes, Mast Cells make the protein dissolving enzymes chymase and tryptase, which can attack joints. Fibrosis of the skin might very well be the remodeling as in that study's title, also related to mast cells.

If you drag a fingernail across the skin of your chest, does that leave a line? (dermatographia)
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
@Countrygirl
If you were to take 500mg of niacin and flush tremendously (I do), that would be a sign of a mast cell problem, because of the excess histamine involved. (IF you can handle that experiment.)

Then in the next one or two days, you'd take quercetin a half hour before and repeat the niacin - for me that almost completely prevents the flush. I had posted some time ago on this subforum some study that said that quercetin works better than prescription drugs.

For me, tart cheery works even better to stabilize the mast cells and prevent them from releasing their inflammatory contents.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
fibrosis of the skin
Here's one from back in 1995 with mice and skin fibrosis:
The role of mast cells in the development of skin fibrosis in tight-skin mutant mice.
https://www.ncbi.nlm.nih.gov/pubmed/7704626
proliferation and activation of MC leads to augmentation of fibrosis

from 2007, again with mice (because they can create mice with no mast cells)
Mast cells and immunological skin diseases.
In the case of scleroderma and chronic graft-vs.-host disease, the function of mast cells in fibrosis is further supported by the ability of these cells and their mediators to induce activation and proliferation of fibroblasts. Therapies targeting mast cells may prove beneficial for treatment of these inflammatory and autoimmune diseases.
 

Countrygirl

Senior Member
Messages
5,429
Location
UK
Thank you for all your replies, Sherlock. I have some studying to do.

Many thanks and if you can point me in the direction of other useful articles, that would be great. Thank you.
 

Countrygirl

Senior Member
Messages
5,429
Location
UK
Thanks ahmo. I am also going to read the thread here on ME as a possible Mast Cell disorder.

I wonder if this is why Dr Bell wrote many years ago that all his ME patients had a history of allergies such as hayfever and asthma? Do any of us not have a childhood history of allergy?
 

Countrygirl

Senior Member
Messages
5,429
Location
UK
@Sherlock @ahmo I am finding this very revealing so far and had no idea that mast cells played (possibly)such a role in my health problems since I was a child. I also have bronchiectasis and glomerulonenephritis and apparently both are thought to be associated with a mast cell activation disorder. Even the exercise-induced hives that I developed when a child is a sign of the over-activity of mast cells. I didn't know anyone else had such an odd reaction to running (those were the days!) Then there are the brown stains on the skin...........................

I don't know if this makes sense, but I had no problems until I had a deep bite by a guinea pig which triggered my first asthma attack and a very itchy rash. From then on I became allergic to so many things, even sun light which causes a rash. The guinea pig died just after she bit me. I think my blood must have poisoned her.
 

Countrygirl

Senior Member
Messages
5,429
Location
UK
I did not.

Do you happen to have a history of bad reactions to bee stings?

The MTHFR SNP?

I have never been stung by a bee, so don't know. I reacted badly to an insect bite (may have been a tick) when I was a student and developed ME shortly after that, but I also had a tetanus jab, and suspect that played a role in suppressing the immune system. I then developed encephalitis from which I never seemed to recover fully.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
I think my blood must have poisoned her.
:woot: :)

but I also had a tetanus jab, and suspect that played a role in suppressing the immune system
I think there are two types of people here: those with weak immunity whose main problem is active infections

and then those mainly with overactive immunity (like me and probably you)

This could be a real milestone for you. I hope it is. Btw, I'd once read that Mast cells were originally called Master cells because they control so much.

Mast cell tryptases and chymases in inflammation and host defense
http://www.ncbi.nlm.nih.gov/pmc/articles/pmid/17498057/

Mast cells and inflammation
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/

Immunomodulation of mast cells by nutrients. 2015
http://www.ncbi.nlm.nih.gov/pubmed/24524883
Abstract

In the past decades an increasing prevalence of allergic disorders was observed in industrialized countries. Thus, it is necessary to develop adequate therapeutic and preventive strategies. Many of the conservative strategies possess diverse harmful side effects. Therefore agents with fewer side effects and a better compliance among afflicted patients would be of interest. Especially substances with natural origin acting immunomodulatory on mast cells - the key effector cells of allergic diseases - could be used. Among them there are components of the daily diet such as distinct fatty acids and amino acids as well as a range of secondary plant substances such as carotenoids, flavonoids and spices. These nutritional substances could be applied as nutraceuticals in the therapy of mast cell associated diseases. Many of these substances show inhibitory influences on the release of prestored mast cell mediators such as histamine or de novo expression of mast cell mediators such as cytokines and eicosanoids which are involved in the pathogenesis of mast cell associated inflammatory conditions like allergic reactions.


Here is another list of MC receptors and agonists: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/table/T1/
...which is from this FFT: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318920/

Note that mast cells have histamine receptors, so IMO that can setup for a vicious cycle which gets started off by MTHFR 677.

Then there are more receptors which are not found on the above two lists, such as for acetaldehyde
http://www.researchgate.net/publica...irway_mast_cells_to_cause_bronchoconstriction
"Acetaldehyde induces histamine release from human airway mast cells to cause bronchoconstriction."
But I now think I was wrong about what is done by the histamine receptors on MCs - I think that they are meant to inhibit more histamine secretion. But what if they go haywire?
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
I don't know if this makes sense, but I had no problems until I had a deep bite by a guinea pig which triggered my first asthma attack and a very itchy rash. From then on I became allergic to so many things, even sun light which causes a rash. The guinea pig died just after she bit me. I think my blood must have poisoned her.
I had a bad cold 6 years ago, which is what set it all off for me.

Sun sensitivity is definitely involved om some immune conditions (lupus is the most famous).
 

ahmo

Senior Member
Messages
4,805
Location
Northcoast NSW, Australia
@Countrygirl Until I started following the pr Mast Cell forum, I knew nothing of them. I only become aware of my significant histamine issues when I went gluten free and started the GAPS diet 3 years ago. I'd had persistent urticaria for years, but before that could only attribute it to pharmaceuticals. From histamine to mast cells, I've since learned that some of my unexplained symptoms are indeed mast cell. They each seem small, but they form a pattern, and seem to be getting more active without my constant vigilance: small ulcer-like lesions in nostrils and ears, waxy exudate "sprayed" in my ears, crystal-like feeling in corners of upper eyes, blood blisters in mouth, and urinary urgency. I think my blotchy skin probably fits in here, altho I've heard a recent description that puts it into a fungal category.

There's a very close connection to adrenal health. When my adrenals are stressed, MC symptoms appear. I've learned a lot from lowhistaminechef.com, although I don't use any of her recipes. Quercetin, royal jelly, rutin, mangosteen, luteolin all are helpful. I now use the symptoms as a monitor to how my system is faring. And I self-test for more of the supps when things are activated. I've also been thrilled with the + effects of Theorharides' formula Neuroprotek, to stop the histamine cascade in the brain. I resisted it when first hearing about it, too expensive...but I've found it fabulous. And it's shown me that when my mind is stuck in a constant chatter mode, I can take one of these and calm it down within 15 minutes.

I don't have a very deep understanding of MC, though enough to cope with my symptoms. However, I'm concerned that there might well be a tendency to increase over time, into some of the more alarming areas, like cardiac, or anaphalyxis. I've been taking low dose naltrexone (LDN) for about 5 months, with greatly increased stamina. I hope maybe some of its benefits spill over into mast cells. I also have over-active, auto-immunity.
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
For many years, my tendons have easily torn and now I have tenosynovitis and De Quervains (both thumbs) in my hands. Is this connected?
Just two nights ago, I had gotten into bed and pulled a heavy blanket across myself. I felt an immediate stab of sharp pain - I had given myself a bad sprain in that thumb. It's taped now as I type this.

(I remember the term De Quervain syndrome because I had researched that last year.)

Last year, my right index finger was so bad and vulnerable that just clicking my mouse injured it some more. So i started using the laptop's touchpad left-mouse button with my left hand instead. There are times when I can't open a tin can -- unless I do it sort of reversed and backwards. My right wrist has been fairly crippled since early December.

I'm mentioning all this so you can compare :)
 

Countrygirl

Senior Member
Messages
5,429
Location
UK
"Sherlock, post: 543181, member: 3969"]I had a bad cold 6 years ago, which is what set it all off for me.

Six years! You're a mere babe!

Thank you for all the great info you have posted for me to read, but it is time for bed here in the UK, so will read it tomorrow. It is very interesting and is new information to me.

A scientist well known to us explained to me that we have a immune deficiency syndrome which puzzled me as I haven't been able to produce the symptoms of a cold for 35 years, since the ME became severe. My immune system appears to kill a virus at fifty paces, which makes me think it is on high alert. In fact, I have no doubt that ME, although destroying my life, yet saved it as the bronchiectasis which is in both lungs was life threatening whenever I had a cold. ME preserved my lungs from further damage.However, I cannot fight bacterial and fungal infections and antibiotics can make me ill, so I guess that reflects a deficiency.

I must hit the hay so will 'see' you tomorrow. Nite, nite! :)
 

Sherlock

Boswellia for lungs and MC stabllizing
Messages
1,287
Location
k8518704 USA
waxy exudate "sprayed" in my ears... and urinary urgency. I
check and check
have you tried anti-inflammatories (like ibuprofen) for the latter? I then get up only every 4 hours instead of every 2 hours (but I don't want to take them every night). Alkalizing strategies like Potassium Citrate capsules also help.

And it's shown me that when my mind is stuck in a constant chatter mode, I can take one of these [Neuroprotek] and calm it down within 15 minutes.
I have recently been very surprised that tart cheery is very anti-anxiety for me.
 

Countrygirl

Senior Member
Messages
5,429
Location
UK
Just two nights ago, I had gotten into bed and pulled a heavy blanket across myself. I felt an immediate stab of sharp pain - I had given myself a bad sprain in that thumb. It's taped now as I type this.

(I remember the term De Quervain syndrome because I had researched that last year.)

Last year, my right index finger was so bad and vulnerable that just clicking my mouse injured it some more. So i started using the laptop's touchpad left-mouse button with my left hand instead. There are times when I can't open a tin can -- unless I do it sort of reversed and backwards. My right wrist has been fairly crippled since early December.

I'm mentioning all this so you can compare :)

Snap!!! Literally! I'm sorry you have this problem too. My tendons react in the same way and are easily damaged. The De Quervain's is intensely painful when it is severe and the thumbs cannot be moved even a quarter inch. I now have to ask the shop assistants to open bottles for me when I buy them and ask passers by to open tins and containers when I need them. Thumbs are very useful........when they work and how I miss them!

I also now have osteopenia and I see that is also listed as part of a mast cell problem.

And I still haven't hit the hay!
 

Countrygirl

Senior Member
Messages
5,429
Location
UK
@Countrygirl Until I started following the pr Mast Cell forum, I knew nothing of them. I only become aware of my significant histamine issues when I went gluten free and started the GAPS diet 3 years ago. I'd had persistent urticaria for years, but before that could only attribute it to pharmaceuticals. From histamine to mast cells, I've since learned that some of my unexplained symptoms are indeed mast cell. They each seem small, but they form a pattern, and seem to be getting more active without my constant vigilance: small ulcer-like lesions in nostrils and ears, waxy exudate "sprayed" in my ears, crystal-like feeling in corners of upper eyes, blood blisters in mouth, and urinary urgency. I think my blotchy skin probably fits in here, altho I've heard a recent description that puts it into a fungal category.

There's a very close connection to adrenal health. When my adrenals are stressed, MC symptoms appear. I've learned a lot from lowhistaminechef.com, although I don't use any of her recipes. Quercetin, royal jelly, rutin, mangosteen, luteolin all are helpful. I now use the symptoms as a monitor to how my system is faring. And I self-test for more of the supps when things are activated. I've also been thrilled with the + effects of Theorharides' formula Neuroprotek, to stop the histamine cascade in the brain. I resisted it when first hearing about it, too expensive...but I've found it fabulous. And it's shown me that when my mind is stuck in a constant chatter mode, I can take one of these and calm it down within 15 minutes.

I don't have a very deep understanding of MC, though enough to cope with my symptoms. However, I'm concerned that there might well be a tendency to increase over time, into some of the more alarming areas, like cardiac, or anaphalyxis. I've been taking low dose naltrexone (LDN) for about 5 months, with greatly increased stamina. I hope maybe some of its benefits spill over into mast cells. I also have over-active, auto-immunity.

I am going to study your post tomorrow as it is too late for me now to think straight. Thank you for sharing this and I look forward to reading it carefully when my grey cell is in a better state.:) I find it fascinating and sounds very familiar and it is good to know we are not alone.:hug:

Nite, nite...............again.