Endothelial cell apotosis in jugular veins of pwMS

[cheerleader]

New, ground-breaking research from Dr. Zamboni's team:

Major endothelial dysfunction and aptosis in the intraluminal septa and defective valves of pwMS----highly deranged when compared to normals.

http://phl.sagepub.com/content/early/20 ... 0.abstract

Why does this matter? A loss of endothelial cells means valves and veins cannot respond to hemodynamic needs of the brain--and would not function properly. Endothelial dysfunction can be overcome---but it will take more than angioplasty to deal with this.
http://ccsviinms.blogspot.com/2014/06/t ... elium.html

cheer

[cheerleader]

Disturbed flow damages and kills endothelial cells in the aortic arch. We understand the mechanism in arteries, but we need more research in veins. Refluxive or irratic flow in blood vessels can kill EC cells. Endothelial cells are essential for maintaining blood flow to organs, as the Columbia University research recently showed us---the brain needs the vascular endothelium to be healthy and functioning, or blood flow is reduced and neurons die.

Here's more on disturbed blood flow
http://ccsviinms.blogspot.com/2010/07/n ... -july.html

"We have developed a model where we disturb blood flow in the carotid artery by partial ligation, and atherosclerosis appears within two weeks," he says. "This rapid progression allows us to demonstrate cause and effect, and to examine the landmark events at the beginning of the process."
Jo says that endothelial cells, which form the inner lining of blood vessels, are equipped with sensors that detect changes in fluid flow.

http://ccsviinms.blogspot.com/2010/07/n ... -july.html

cheer

[ThisIsMA]

Thanks Cheer for posting this new Dr. Zamboni research! Here is a quote from the abstract:

Results The internal jugular veins’ wall showed a significant derangement of the endothelial layer as compared to controls. Surprisingly, no endothelial cells were found in the defective cusps, and the surface of the structure is covered by a fibro-reticular lamina.

I added bold and Italics to the beginning of the second sentence for emphasis. Wow, the finding of no endothelial cells being present is really disturbing. ...And provides all the more reason for me to follow an endothelial health program, to at least try to save what endothelium I still have and possibly help restore what I don't have!

I wonder what a *cusp* is, as used in the above quoted bold italic text? I've never heard that word used in this context.

...O.K. I just looked it up. According to http://www.merriam-webster.com/dictionary/cusp , cusp means:

a pointed end or part where two curves meet

But it also can mean:

a fold or flap of a cardiac valve

maybe that's what *cusp* means in this context?

M.A.

[Cece]

Surprisingly, no endothelial cells were found in the defective cusps

By cusps, I think it means the cusps of the valve which would be the flaps.

The cusps are the moving part in this animation:

It seems to me that the abnormal valves were already a lost cause and so the finding of no endothelial cells there, which is an indication of deranged hemodyamics, is another confirmation of what was already seen since hemodynamics are already being imaged using ultrasound, MRV, venography, etc. It does tell us that the bad hemodynamics is having an effect on the endothelium but it could be only in that specific area. We need to know how bad the endothelium is in the rest of the jugular vein and, especially, in the venules and capillaries of the brain that make up the blood-brain barrier.

[ThisIsMA]

Good points, Cece. Here's another phrase from that study I'm trying to understand:

the surface of the structure is covered by a fibro-reticular lamina

I googled the phrase *reticular lamina* and the webpage http://medical-dictionary.thefreedictio ... lar+lamina gave this definition:

reticular lamina a layer of the basement membrane, adjacent to the connective tissue, seen in some epithelia; it is of variable thickness and is composed of condensed connective tissue with a reticulum of collagen fibers.

And here's the scary part: the word *reticulum* is defined from the same website as:

1. A netlike formation or structure; a network.

Also from the same website, the phrase *basement membrane* is defined as:

basement membrane a sheet of amorphous extracellular material upon which the basal surfaces of epithelial cells rest; it is also associated with muscle cells, Schwann cells, fat cells, and capillaries, interposed between the cellular elements and the underlying connective layer.

The word *lamina* is defined as:

layer; a thin, flat plate of a larger composite structure.

And the word *epithelium* is defined as:

epithelium [ep″ĭ-the´le-um] (pl. epithe´lia) (Gr.)
the cellular covering of internal and external surfaces of the body, including the lining of vessels and other small cavities. It consists of cells joined by small amounts of cementing substances. Epithelium is classified into types on the basis of the number of layers deep and the shape of the superficial cells.

Anyway, if the endothelial cells in the cusps of the valves have been replaced by a reticulum (netlike formation), could that explain why the blood brain barrier is leaking?

I am just speculating here as a person with MS, I am NOT a professional. We are SO LUCKY that Dr. Zamboni is looking into these things!

I wonder what the difference is between endothelium and epithelium. They sound like synonyms. Maybe endothelium is the type of epithelium that lines blood vessel walls?

So if I'm understanding this correctly, the bottom layer of the inner lining of the internal jugular veins has been replaced in the cusps of the valves, by a net of collogen fiber cells.

[cheerleader]

If endothelial cells maintain bloodflow, (as we are now learning from researchers at Columbia Un.)--then how would a loss of these cells affect a valve or vein's ability to open/close and maintain cerebral blood flow? This "derangement" (Dr. Zamboni's word) in the jugular vein would be damaging.

This cellular loss, and the higher levels of ET 1 in the plasma, is also a clue that there is endothelial dysfunction, which may be systemic and could be affecting other parts of the body, as Cece mentioned, like the blood brain barrier. Further studies will elucidate how widespread the loss of endothelial cells is in pwMS. I saw problems with petechial lesions on Jeff's legs, high coagulation numbers in his plasma and high enzymes in his liver...which lead me to consider systemic endothelial dysfunction. http://ccsvi.org/index.php/helping-myse ... ial-health

ThisIsMA--You're right! Endothelial cells are simply a specialized type of epithelial cell---since they only line blood vessels.
cheer

[NHE]

I wonder what the difference is between endothelium and epithelium. They sound like synonyms. Maybe endothelium is the type of epithelium that lines blood vessel walls?

The prefix endo means inside. The endothelium is a cell layer that lines body cavities that are only exposed to environs that are inside the body, i.e., blood vessels. The prefix epi means outside. The epithelium is a cell layer that lines parts exposed to the outside environs. The skin epithelium is an obvious example. However, the lungs and the digestive tract epithelium are two other examples.

[frodo]

This finding looks specially related to the Endothelin-1 problem

http://www.thisisms.com/forum/chronic-c ... 15731.html

224% higher in patients than controls!!! And that is the average!! I wonder why there is so little research in this field. Maybe because it cannot be explained by auto-immunity?

By the way, other interesting article

Cerebral hypoperfusion in multiple sclerosis is reversible and mediated by endothelin-1

http://www.ncbi.nlm.nih.gov/pubmed/23509249

[cheerleader]

Just want to explain a little bit more, because this is important stuff when looking at CCSVI.

Frodo--yes, you're right. Higher levels of endothelin 1 are found in pwMS. And there actually has been alot of research on this, just not in MS, but in stroke. Here's some of my blog post on the topic.

In the news--- Newly discovered peptide, blocks remyelination!! Stopping this process repairs MS damage.
http://www.natureworldnews.com/articles ... tients.htm

What's this "new" peptide we want to block?
It's called endothelin-1 or ET-1, and it's released by the astrocytes maintaining the endothelial layer of your blood brain barrier.
http://www.cell.com/neuron/abstract/S08 ... 13)01083-0

We've known about ET-1 for years. It's not only found in MS.
Endothelin-1 is raised in situations where there is endothelial distress. When endothelial cells are hurt by ischemia and oxidative stress, and nitric oxide levels are low. ET-1 creates vasoconstriction, is pro-inflammatory, pro-fibrotic and slows blood flow. Which would explain why it inhibits remyelination. Yet not one single press release on this exciting new MS discovery mentioned this important fact, or what causes ET-1 levels to be high in the first place.

As you might expect, plasma ET-1 levels are very high in ischemic stroke.
http://stroke.ahajournals.org/content/2 ... 4.full.pdf

ET-1 released by astrocytes is seen after subarachnoid hemorrhage
http://www.biomedcentral.com/1471-2202/14/131

Serum levels of ET-1 are used as a marker of cerebral ischemia
http://www.intmed.ro/attach/rjim/2010/rjim410/art06.pdf

And Endothelin 1 serum levels are through the roof in people with MS----

The plasma ET-1 levels were, on average, 224% higher in the patients with MS than in the controls (p < 0.005). The mean ET-1 levels (mean +/- standard deviation [SD]) were 3.5 +/- 0.83 pg/mL (min 2.13, max 5.37 pg/mL) in patients with MS and 1.56 +/- 0.3 pg/mL (min 0.9, max 2.13 pg/mL) in healthy volunteers. Neither the different forms nor stages of MS had an influence on the results. The ET-1 level was also not correlated with the duration of the disease.
http://www.ncbi.nlm.nih.gov/pubmed/11315981

http://ccsviinms.blogspot.com/2014/02/e ... dence.html

So....what does this all mean? How does it fit in with what Dr. Zamboni found---that there is death of endothelial cells in the veins and valves of people with CCSVI?
It simply means that endothelial dysfunction is a huge part of the MS disease process. There is a vascular connection to MS and cerebral blood flow.
The evidence is there---
cheer

[Cece]

It simply means that endothelial dysfunction is a huge part of the MS disease process.

Yes, this!
I don't know if targeting endothelin-1 will improve the health of pwMS, but I am excited to see it researched.

[cheerleader]

bump---for ElliotB and his blood flow thread in general discussions...

[1eye]

bump---for ElliotB and his blood flow thread in general discussions...

Major endothelial dysfunction and aptosis in the intraluminal septa and defective valves of pwMS----highly deranged when compared to normals.

http://phl.sagepub.com/content/early/20 ... 0.abstract

They cannot exclude past injury that has healed up (happens when you over-balloon), It's possibly scar tissue. Injuries to the jugs can happen in lots of ways, and you don't even get immediately sick. Such as if you throw your head right to left many times very quickly (like the Muppet "Animal'') when hearing a fast song. Jugs have some redundancies because they are not used much when we are upright. So even if they thrombose, we may not get sick immediately, and may not connect the two events.

The paper also says we have to pay special attention to post-procedure medication protocols, because of the possibility of thrombosis. Are balloons more likely to cause scarring in veins than arteries? I would expect so, but don't know.

I would also think, expand slowly, get out quickly might help, but its probably a good thing I don't make such choices