Connective Tissue Disorders, Collagen and CCSVI

A forum to discuss Chronic Cerebrospinal Venous Insufficiency and its relationship to Multiple Sclerosis.

Postby Rose2 » Sun Sep 05, 2010 2:40 pm

Wow again, Cheer!
When do you eat? ;) Thanks so much for your continuing work.
This vein quality issue is intriguing to me in that on my Maternal side, for as far back as I have information, several generations, there has been an 'inherited' leg vericous vein problem in many of the women. I do not have the leg vericous vein problem, but I had MS! I no longer have MS as I have been Liberated. :lol:
I have 3 maternal cousins with MS now. My mother and sisters had to have their leg vericous veins 'strippped' out at a relatively young age.
There is now suspicion that earlier generations of women had undiagnosed MS, with the history we have to piece it together. It makes sense.
None of this is on my fraternal side.
Just my 2 cents.
Sincerly, Rose2 ;)
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Collagen shifts in vein walls found in CCSVI

Postby cheerleader » Sat Mar 19, 2011 2:16 pm

Dr. Gabbiani again presented updated research on the collagen shift from type I to type III found in the jugular veins of pwCCSVI. Here is a great thread where we discussed this last year-----
http://www.thisisms.com/ftopict-11311-.html

This collagen shift is very, very important to understand. Collagen I is more pliant, Collagen III is stiffer, has more fibrin. It is found in scar tissue. Dr. Gabbiani believes the shift is from hemodynamic changes due to reflux and disturbed blood flow.

All specimens from CCSVI veins showed: 1) thickening and sclerosis of the adventitia, 2) a significant difference of birefringence pattern, from a green birefringence to a red birefringence (P<0.001), between veins of CCSVI patients and those of controls, suggesting a switch from collagen type I to collagen type III expression; this modulation was confirmed by means of collagen type immunohistochemistry.
CONCLUSIONS
It appears that the changes affecting CCSVI veins in MS patients concern mainly the extracellular matrix, collagen in particular. The switch in collagen type from a prevalence of type I to a prevalence of type III may be implicated in the hemodynamic changes obseved in these patients.

http://ccsvism.xoom.it/ISNVD/Abstract-Gabbiani.pdf

It is important to note that this exact same shift is found in varicose veins and chronic venous insufficiency

Abstract
STUDY OBJECTIVES: The connective tissue alterations in varicose vein wall are supposed to be one of the main causes of primary varicose vein (main sign of human lower limbs chronic venous insufficency).

METHODS: 5 varicose vein samples from 5 patients undergoing stripping surgery of long saphenous vein were compared with 5 control samples of healthy (non-dilated) long saphenous veins from necroptic material (with no history of varicosis). They were fixed in a Baker solution, processed by use of light microscopic method, cut to ultra-thin sections (4-5 microm) and stained with PicroSirius Red for collagen. Sections were scanned with light microscope (Leica, Germany) and camera Canon S50 (Germany) and analysed by morphometric programme Image J v.1.38g (National Institute of Health, USA).

RESULTS: In the group of healthy (non-dilated) veins the mean collagen I/III ratio value was 31.40 and in the group of varicose veins the mean collagen I/III ratio was 12.35; the difference is statistically significant: healthy veins contain significantly more of collagen subtype I and varicose veins contain significantly more of collagen subtype III in their walls.

CONCLUSION: The statistically significant difference in the collagen I/III ratio between the groups of healthy (non-dilated) and varicose (dilated) vein walls is worthy of further following.


Type III collagen shift also shows up in VOC--veno-occlusive disease of the liver, like Budd-Chiari
link

Also important to note that collagen III is more often found in arteries, and not found in healthy veins. It provides stiffness and structure to arteries, and is also involved in thrombosis and arteriosclerosis. Dr. Lee mentioned in '09 in Bologna-he was surprised to learn collagen III could show up in veins.

I believe this is why people are seeing thrombosis and restenosis occuring more in CCSVI treatment than in other venous interventions. Because the collagen has shifted prior to intevention, and the vein is already more susceptable to injury. I harken back to Dr. Dake's first impressions of Jeff's veins..."I've never seen anything like these veins before."
cheer
Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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collagen

Postby zinamaria » Sat Mar 19, 2011 2:33 pm

Now this really makes sense! Thanks for posting, cheer.
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Postby Cece » Sat Mar 19, 2011 2:55 pm

I asked this before, I think the answer was yes, if it is possible for the collagen to switch back to the healthier collagen 1 if good blood flow has been restored? My other thought is if it is throughout the jugular that this shift has occurred or if it is only at the area of stenosis? Has such a shift occurred higher up, such as in the deep cerebral veins?

I wonder if you are right and this turns out to be a factor in why people have restenosis and complications! Very interesting.

I love all the material coming out of ISNVD....
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Postby Rokkit » Sat Mar 19, 2011 3:06 pm

I'm also wondering if this is why the stenoses seem to progress. Some studies are correlating age and degree of disease progression with severity of stenoses. Could it be that the years of insult produced by reflux and altered hemodynamics resulting in slow, ongoing collagen shift is what accounts for the progression of CCSVI and MS?
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Postby cheerleader » Sun Mar 20, 2011 10:10 am

Rokkit wrote:I'm also wondering if this is why the stenoses seem to progress. Some studies are correlating age and degree of disease progression with severity of stenoses. Could it be that the years of insult produced by reflux and altered hemodynamics resulting in slow, ongoing collagen shift is what accounts for the progression of CCSVI and MS?


Exactly right, Rokkit. We see this in cardiovascular disease, where disturbed blood flow changes the lining of the artery over time, and eventually leads to stroke or heart attack.

CCSVI is a progressive disease. Years of altered hemodynamics create hardened, stiff and stenosed veins. BUT, most likely, the venous malformation is there from the beginning. It is the altered flow + severity of VM + time which creates MS progression.

Cece, we don't know yet is venoplasty creates a switch back. Dr. Gabbiani and others will be looking at that. We do know that health shear stress and flow enhances endothelial function and allows for healing, but to what degree is just not known yet-
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Husband dx RRMS 3/07
dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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Postby ozarkcanoer » Sun Mar 20, 2011 1:49 pm

It is interesting to me that collagen III is found in scar tissue. Last week I found out, much to my dismay, that the stent in my left IJV is completely occluded by scar tissue. I wonder if that means that the collagen at that location is/was collagen III. Dr Haskal told me that scarring can occur at stent sites. This scar tissue is almost impossible to drill through with a diamond tipped drill. I know of one other of Dr H's patients with exactly the same problem. Something to think about when considering stents right now. I have a neighbor who was a stent salesman (what a coincidence). He told me that the medicated stents are used to prevent this scarring.

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Postby Brightspot » Sun Mar 20, 2011 3:28 pm

great read, thanks for the post and links
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Zamboni ISET .pdf online

Postby CureIous » Sun Mar 20, 2011 5:12 pm

Didn't find a post about this, spent 20 min searching so don't shoot the messenger, this makes a great printout if you have the ink (I do). No, it's not a research paper, but a paper copy if you will of his powerpoint presentation, and very illustrative.


http://www.iset.org/files/content/event ... 142300.pdf

Just happened upon it while looking for good jugular venous return stuff. If it's already been posted, as most stuff on here has, I truly and sincerely apologize. Otherwise, I think it's relevant especially for those of us who are visual learners.

Mark
RRMS Dx'd 2007, first episode 2004. Bilateral stent placement, 3 on left, 1 stent on right, at Stanford August 2009. Watch my operation video: http://www.youtube.com/watch?v=cwc6QlLVtko, Virtually symptom free since, no relap
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Postby Cece » Sun Mar 20, 2011 5:49 pm

With the right search words, you can find them from all the CCSVI presenters at ISET. It's not actually his presentation, it's the slides and whatever was turned in ahead of time to ISET, but they finish up their work on the presentations more at the last minute, so some of what is in these ISET files did not make it into the actual presentations. It is an IT error, I believe, that these were posted by ISET and made available in google search results like this. It's why I haven't linked to it directly before. Fantastic material. Did you see the tricuspid valve malformation? And the sideways valve, both in the venogram image and then cut out as an actual tissue sample? Remarkable.
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Postby MsMezza » Sun Mar 20, 2011 6:12 pm

fantastic !!!

CCSVI researchers are definately heading in the right direction!!!!!!!!
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Postby CureIous » Sun Mar 20, 2011 7:09 pm

Cece wrote:With the right search words, you can find them from all the CCSVI presenters at ISET. It's not actually his presentation, it's the slides and whatever was turned in ahead of time to ISET, but they finish up their work on the presentations more at the last minute, so some of what is in these ISET files did not make it into the actual presentations. It is an IT error, I believe, that these were posted by ISET and made available in google search results like this. It's why I haven't linked to it directly before. Fantastic material. Did you see the tricuspid valve malformation? And the sideways valve, both in the venogram image and then cut out as an actual tissue sample? Remarkable.


Yeah, I really dug it for the visual representations of things we discuss frequently, what you mentioned, the collagen III pics, and especially the visual on how/why the venous circles fill and in what order, plus the reminder that there is just a wee bit of leftover arterial pressure which adds to the venous pressure etc etc.

Was actually looking up stuff related to venous pressure when I found it. Image

Circulation, fluid dynamics, Starling forces, capillary beds, so intriguing and fascinating the interplay. Hopefully the current research will lead to entire new areas of investigation, esp. as it pertains to the BBB and the exact causitive forces behind it's breach (though of course it is inferred at this point via CCSVI).

More stuff to dump in my lunchbox... :)

(if you want another fascinating read, check out wiki about collagen, scleroproteins, and how they fold the hydrophobic portions to the inside and the structure becomes basically water insoluble, almost like bone. When I read of things like "a clot that a diamond tipped drill can't get through", seems like it ties in with this, as scleroproteins and their functions are what makes bone, muscle fiber, and other "permanent" matrixes what they are, and indeed may play a precipitous role in what we are seeing with scar formations and the aftermath of venous insults caused by stretching, tearing, stents and the like, maybe someday we will have something that can be tested and counteracted against in respect to the Collagen III in our veins, if even for a short time of proper healing?)
RRMS Dx'd 2007, first episode 2004. Bilateral stent placement, 3 on left, 1 stent on right, at Stanford August 2009. Watch my operation video: http://www.youtube.com/watch?v=cwc6QlLVtko, Virtually symptom free since, no relap
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Postby Cece » Sun Mar 20, 2011 7:47 pm

There's so much to learn, I'm not there yet. The concept of Starling resistor was a new one for me from ISNVD. I've looked at the visual on the order that the venous circles fill or empty but don't have that grasped yet. The collagen III pics!! Those were impressive, you can see the difference, this is real what we are talking about.

Try searching for "Dake Iset PDF" or "Haskal ISET pdf"....
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Postby ikulo » Sun Mar 20, 2011 8:23 pm

For those interested in the Dake ISET presentation: http://www.iset.org/files/content/event ... 075234.pdf
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Postby CureIous » Sun Mar 20, 2011 8:37 pm

ikulo wrote:For those interested in the Dake ISET presentation: http://www.iset.org/files/content/event ... 075234.pdf


Great link, just blew through that one. Lots of great info and commentary. Thanks for the link..
RRMS Dx'd 2007, first episode 2004. Bilateral stent placement, 3 on left, 1 stent on right, at Stanford August 2009. Watch my operation video: http://www.youtube.com/watch?v=cwc6QlLVtko, Virtually symptom free since, no relap
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