Update Sept. 2013 ---New research links high levels of ET-1 to changes in cerebral microcirculation and increased vulnerability of the brain. People with MS have ET-1 levels which are found to be 224% higher than normal people.
http://www.ncbi.nlm.nih.gov/pubmed/23959559
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Recent research is showing just how important blood flow is to people with MS.
We'll discuss a new study that looked at cerebral perfusion (blood going through the brain) and found that it was linked to levels of endothelin-1 (ET-1) in the blood.
For new members, the endothelium is the layer of cells lining your blood vessels. It is the largest organ in our bodies, lining 60,000 miles of veins, arteries, capillaries and blood vessels. (see pic)
Endothelin 1 is a protein and a potent vasoconstrictor, meaning it closes down blood vessels and slows blood flow. It is released by the endothelium. Increased levels of ET-1 are related to endothelial dysfunction in stroke, cardiovascular disease, diabetes and inflammation.
http://cardiovascres.oxfordjournals.org/content/76/1/8.full
And people with MS have ET-1 levels that are 224% higher than normal people. (!!!!)
http://www.ncbi.nlm.nih.gov/pubmed/11315981
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Here's the new study which is continuing on with this research in MS and linking it to cerebral blood flow.
http://www.ncbi.nlm.nih.gov/pubmed/23509249
Decreased cerebral blood flow (CBF) may contribute to the pathology of multiple sclerosis (MS), but the underlying mechanism is unknown.
We investigated whether the potent vasoconstrictor endothelin-1 (ET-1) is involved. We found that, compared with controls, plasma ET-1 levels in patients with MS were significantly elevated in blood drawn from the internal jugular vein and a peripheral vein.
(this confirms what the study in 2001 showed us, ET-1 levels are abnormally high in pwMS)
The jugular vein/peripheral vein ratio was 1.4 in patients with MS vs. 1.1 in control subjects, suggesting that, in MS, ET-1 is released from the brain to the cerebral circulation. Next, we performed ET-1 immunohistochemistry on postmortem white matter brain samples and found that the likely source of ET-1 release are reactive astrocytes in MS plaques. We then used arterial spin-labeling MRI to noninvasively measure CBF and assess the effect of the administration of the ET-1 antagonist bosentan. CBF was significantly lower in patients with MS than in control subjects and increased to control values after bosentan administration. These data demonstrate that reduced CBF in MS is mediated by ET-1, which is likely released in the cerebral circulation from reactive astrocytes in plaques. Restoring CBF by interfering with the ET-1 system warrants further investigation as a potential new therapeutic target for MS.
The researchers are guessing that the high levels of ET-1 in plasma of pwMS is due to reactive astrocytes in MS lesions, caused by some mystery mechanism. They say that it is "suggested" that ET-1 might be released by the brain. Their guess is that lesions release ET-1, which created hypoperfusion in the brain. They don't really know for sure what is causing ET-1 levels to be so high, which is why they say "likely."
A more plausible theory is that slowed cerebral blood flow, caused by CCSVI, is creating an hypoxic/ischemic situation in the brain, releasing ET-1 into the blood stream and activating the immune system.
It is a scientific fact that people who have strokes have higher levels of ET-1 in their plasma. Just like pwMS. Ischemic injury causes ET-1 levels to rise dramatically. http://stroke.ahajournals.org/content/23/7/1014.full.pdf
All the study really showed was the pwMS have higher levels of ET-1 and ET-1 causes slowed cerebral bloodflow---the rest is their attempt to make this fit the current autoimmune model of MS, rather than look at the VASCULAR evidence.
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Endothelial dysfunction and high ET-1 levels can be caused by many factors. ET-1 can be elevated due to ischemia, or low oxygen. Levels can be elevated in those with diabetes, or in those who are obese. They can be elevated in those who eat high fat diets or live in industrialized countries. All we know for sure is that high ET-1 levels show the endothelium is in distress.
And high ET-1 levels are NOT good for your cerebral blood flow.
Long time readers of this page know that this has been my focus since Jeff was diagnosed in 2007. What researchers will be looking at is how they can make a drug to reduce ET-1 in your blood, to help restore cerebral circulation. That's what they did in the study, using ET-1 antagonist drug, bosentan. Because they can patent it, and sell it as an new MS treatment (!) ...side effects may include liver damage and anemia.
But I think that's simply bass-akwards.
Why not learn to how limit endothelial dysfunction? Why not learn what measures can heal the endothelium and decrease ET-1?
Because there are things you can do today to lower your levels of endothelial dysfunction, and potentially decrease ET-1 levels.
If you haven't checked out the program, look at it, take it to your doctor or naturopath.
link to the Endothelial Health Program
and be well,
Joan
