E1 and vascular remodeling

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

E1 and vascular remodeling

Postby MegansMom » Tue Jul 19, 2011 4:25 am

E1 (Endothelin 1) is found at more than double of the normal amount in pwMS.
(see study in "Neurology" 2001) this has been validated but the cause was not determined ( seems to be yet another vascular clue ignored)

Endothelin levels rise when the endothelium cells are triggered by 3 things: low oxygen ( hypoxia) , low glucose ( hypoglycemia) and interrupted sheer stress ( turbulence in blood vessels).

CCSVI could create the environment if all three triggers.

Endothelin1 causes vascular remodeling- that means that it changes the vessel walls including valves. It causes vessels to become:

More fibrotic ( stiff)
More hypertrophic (thickened)

In CCSVI this would be chronic and the effect may continue AFTER VENOPLASTY?

I believe these clinical trials of " before" and "after" assessments should be doing a simple E1 assay blood test, so we can see if the E1 level is the cause of restenosis.

Why not add this simple test to see what the E1 level is at all points - pre-and post- liberation?

It seems to me that the researchers could find out more information for a relatively inexpensive cost, instead of doing it years from now.

We need to uncover the culprit of the remodeling. Could It be E1? Just an idea.

http://circ.ahajournals.org/content/110 ... 3.abstract
Last edited by MegansMom on Sun Jul 24, 2011 3:46 am, edited 1 time in total.
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My 35 yo daughter is newly dx 8/19/10 (had 12 symptoms)
Dx with Type A CCSVI- 1 IJV & double "candy wrapper" appearance of her Azygos
Venoplasty done Sept 21, 2010
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Postby Cece » Tue Jul 19, 2011 5:42 am

I would like to know if my E1 levels have gone down!
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Postby pairOdime » Tue Jul 19, 2011 6:08 am

Same here....I would like to know as well. Checking E1 levels pre- & post- CCSVI venoplasty seems like an excellent idea to me. Wasn't the average E1 level for pwMS around 224% as noted in previous research?
It's a paradigm shift
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Postby MegansMom » Tue Jul 19, 2011 6:14 am

pairOdime wrote:Same here....I would like to know as well. Checking E1 levels pre- & post- CCSVI venoplasty seems like an excellent idea to me. Wasn't the average E1 level for pwMS around 224% as noted in previous research?


That is correct it was 224% in the study done by NEUROLOGISTS ! you would have thought that they would have seen the word Endothelium in Endothelin ?
Cat (Catherine Somerville on FB)
MegansMom
My 35 yo daughter is newly dx 8/19/10 (had 12 symptoms)
Dx with Type A CCSVI- 1 IJV & double "candy wrapper" appearance of her Azygos
Venoplasty done Sept 21, 2010
Doing extremely well-
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Postby munchkin » Tue Jul 19, 2011 6:17 am

Would this be a blood test that a GP could order or is it a very specific test?
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Postby PointsNorth » Tue Jul 19, 2011 7:54 am

I will be treated (2nd time) in 2-1/2 weeks. I will try to have GP (family doctor) order this test. And then do a follow up test 2 weeks later. Maybe others are interested? Highly unscientific but we can amass some prelim findings. Think of it as medical crowdsourcing.

Perhaps some medico could design a very simple research protocol that we could strive for? All with the aim of garnering more interest in the subject.

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Postby Cece » Tue Jul 19, 2011 8:13 am

PointsNorth, I am very interested in what you might find. I wonder if your doctor will be cooperative!

Best case scenario would be if there were a marked, measureable drop post-procedure. If it is cheap enough, it could even be something to keep tabs on in the months post-procedure. If the endothelin starts creeping up again, it could be an indicator of restenosis.
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Postby Thekla » Tue Jul 19, 2011 9:47 am

this is fascinating. Are there dietary approaches that would support this after treatment?
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Postby David1949 » Tue Jul 19, 2011 12:51 pm

Do you have a link to the study in "Neurology" 2001?
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Postby pairOdime » Tue Jul 19, 2011 1:02 pm

http://www.ncbi.nlm.nih.gov/pubmed/11315981

J Neuroophthalmol. 2001 Mar;21(1):37-8.
Increased endothelin-1 plasma levels in patients with multiple sclerosis.
Haufschild T, Shaw SG, Kesselring J, Flammer J.

University Eye Clinic, Basel, Switzerland.

OBJECTIVE:
We tested the hypothesis that the plasma level of endothelin-1 (ET-1) is increased in patients with multiple sclerosis (MS). The peptide ET-1 is one of the most potent known vasoconstrictors. An increased level of endothelin could explain some of the vascular symptoms of these patients.

MATERIALS AND METHODS:
A specific radioimmunoassay was used to determine ET-1 plasma levels. Twenty patients with MSwere compared to 20 age- and sex-pair-matched healthy subjects.

RESULTS:
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 MSand 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.

CONCLUSIONS:
The plasma ET-1 level is markedly and significantly increased in patients with MS. Neither the cause of such an increase nor the pathogenetic role is known.
It's a paradigm shift
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Postby Cece » Tue Jul 19, 2011 1:24 pm

This article cited the endothelin-1 article:
Neurosci. 2009 Aug 12;29(32):10047-62.
Endothelin-1 regulates oligodendrocyte development.
Gadea A, Aguirre A, Haydar TF, Gallo V.
SourceCenter for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.

Abstract
In the postnatal brain, oligodendrocyte progenitor cells (OPCs) arise from the subventricular zone (SVZ) and migrate into the developing white matter, where they differentiate into oligodendrocytes and myelinate axons. The mechanisms regulating OPC migration and differentiation are not fully defined. The present study demonstrates that endothelin-1 (ET-1) is an astrocyte-derived signal that regulates OPC migration and differentiation. OPCs in vivo and in culture express functional ET(A) and ET(B) receptors, which mediate ET-1-induced ERK (extracellular signal-regulated kinase) and CREB (cAMP response element-binding protein) phosphorylation. ET-1 exerts both chemotactic and chemokinetic effects on OPCs to enhance cell migration; it also prevents lineage progression from the O4(+) to the O1(+) stage without affecting cell proliferation. Astrocyte-conditioned medium stimulates OPC migration in culture through ET receptor activation, whereas multiphoton time-lapse imaging shows that selective ET receptor antagonists or anti-ET-1 antibodies inhibit OPC migration from the SVZ. Inhibition of ET receptor activity also derepresses OPC differentiation in the corpus callosum in slice cultures. Our findings indicate that ET-1 is a soluble astrocyte-derived signal that regulates OPC migration and differentiation during development.

Can anyone interpret from that just how endothelin-1 affects oligodendrocytes? Since oligodendrocytes make myelin, this would seem to be relevant.
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Aerobic exercise training reduces plasma endothelin-1

Postby ThisIsMA » Wed Jul 20, 2011 12:05 am

Hi Cece,

I couldn't "translate" that last study you quoted, although I agree that it is probably relevant. They used a lot of confusing double negatives that really threw me though.

Meanwhile, I found this study:

http://jap.physiology.org/content/95/1/336.short

Aerobic exercise training reduces plasma endothelin-1 concentration in older women

So it looks like this is one way we could reduce our ET-1 levels (for those of us who are able to exercise).

Ironic that most of us suffer from fatigue, making exercise difficult, even without our other maladies...

Here's a quote from the above study:

we also measured plasma ET-1 concentration after 3 mo of aerobic exercise (cycling on a leg ergometer at 80% of ventilatory threshold for 30 min, 5 days/wk). Regular exercise significantly decreased plasma ET-1 concentration in the healthy older women (2.22 ± 0.16 pg/ml, P < 0.01) and also significantly reduced their blood pressure.


Oh, also, correct me if I'm wrong (which I might be) but I think having ET-1 of 224% of normal is a little more than two times the normal level, not hundreds of times the normal level. Am I right about that? I would think that 100% of normal would mean normal, and 200% of normal would mean 2 times normal. It seems like even that amount of increase in ET-1would be very significant!

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Postby Cece » Wed Jul 20, 2011 6:13 am

I forgot to mention that the one that I quoted was one of the few studies that cited the endothelin-1 article.

This aerobic research is interesting! So rather than worry about my endothelin levels, I should get up and work out? :)

Doesn't it always come back down to exercise and diet. (And venoplasty.)

This also might contribute or be a marker for the worsening of the endothelium as we age:
We previously reported significantly higher plasma ET-1 concentration in middle-aged than in young humans
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Postby PointsNorth » Wed Jul 20, 2011 4:18 pm

We previously reported significantly higher plasma ET-1 concentration in middle-aged than in young humans


Refuse to age. Just say no to higher plasma ET-1 concentrations.

Approached my doc today and she said that she was not sure they could even test for ET-1. I won't see neuro till after procedure, but peraps I could convince him? Wishful thinking. :? I would've liked a before/after comparison.

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Postby Cece » Wed Jul 20, 2011 4:24 pm

www.mpbio.com/product_info.php?open=&cP ... ountry=223
Toxic peptides from a snake venom, the sarafotoxins, show structural and functional homology to Endothelin-1.

8O
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