The Endothelium

Update  APRIL 2019
More research continues to come in, linking endothelial dysfunction to multiple sclerosis.  Pub med has hundreds of new papers. 
https://www.ncbi.nlm.nih.gov/pubmed/?term=multiple+sclerosis+endothelial+dysfunction

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When I first began looking into how Jeff's MS was related to his vascular system in 2007,  I read many papers on pubmed which discussed the "endothelium."  A dysfunction in the lining of our blood vessels was implicated in chronic diseases of inflammation and hypoperfusion, such as MS.  I noticed that there were many modern day environmental factors that caused problems with endothelial health and blood flow.  Endothelial dysfunction was linked to diabetes, cardiovascular disease, autoimmune disease and neurodegenerative disease.  

Fast-forward seven years, and there are health stories on the endothelium in the mainstream press every day.  Here's a sampling from just last week----

Tomato Sauce helps fight heart disease   Of 36 patients with heart disease, those taking the pill every day for two months saw their blood vessels widen by 53 per cent.  This was due to improved functioning of the endothelium, the inner wall cell lining of blood vessels, scientists believe. link

How the brain regulates blood flow   Hillman found that the vascular endothelium, the inner layer of blood vessels, plays a critical role in propagating and shaping the blood flow response to local neuronal activity. While the vascular endothelium is known to do this in other areas of the body, until now the brain was thought to use a different, more specialized mechanism and researchers in the field were focused on the cells surrounding the vessels in the brain.link

Eating Strawberries may lower blood pressure   Strawberries are rich in antioxidants, which may lower blood pressure by relaxing the endothelium, the lining inside blood vessels.  Relaxing the endothelium widens the arteries, reducing pressure.link

So, now that we know the endothelium is truly important---how is our current environment impacting our health?   And what can we do about it?
Here's what I wrote in 2007:

                                                            

I truly believe endothelial dysfunction is the disease of modern man, and is responsible for the increasing rates of chronic disease in industrialized nations.

To provide a contrast and by means of example, I present a day in the life of two women, separated by only 200 years in time.

19th Century- Life as it been lived for thousands of years-

You and your husband get up from bed as the sun rises and the rooster crows. You both get dressed and head outside together to milk the cows and feed the livestock. You work the pump at the well, get a drink of water, which comes from a fresh spring underground. The physical exertion of pumping water and carrying it, lifting the feed and milking the cows has worked up a good sweat. You gather some fresh eggs from the henhouse, and head inside to cook breakfast. The meal includes coffee or tea made with spring water, fresh milk from the cow, eggs and toast with apple preserves, jarred last fall.

The children rise, get dressed, eat and are soon out the door to walk to school. Your husband heads off to his work in the barn. There is laundry to be washed and hung on the line and gardening to do. You spend over two hours out doors, in the sunshine.  Again, hard work and more exercise. This is not a life of leisure!

Fresh fruits and vegetables are eaten in season and canned and jarred for off season.  There isnʼt much meat, but an occasional fish from the stream or chicken from the henhouse. Grains are whole, and you add flaxseed to the bread. Root vegetables and greens are plentiful. Mealtime is spent together as a family. After dinner, and after the dishes pots and pans are cleaned, the family sits together and reads or plays board games. Soon the sun sets and itʼs time for bed. Everyone is tired from the dayʼs activities and ready to sleep.

21st Century--Our Modern Life

You rise in the dark to the incessant buzz of the alarm clock. Itʼs a quick shower in chlorinated and fluoridated city water and blow dry before heading to the kitchen to make a pot of coffee. You get your water from the tap and microwave a breakfast sandwich of processed ham and cheese to go. You check your e-mail on the laptop and holler to wake your husband and the kids and hurry them up- thereʼs no time to waste! They get dressed, grab their backpacks and eat their microwaved breakfasts as everyone piles into the van.

Itʼs off to school where you drop them at the door. Then you get back on the freeway to sit in traffic. Love those fumes! Youʼre starting to get a headache. Trapped on the road, you try to make good use the time by calling clients and checking your phone. Your stress levels are now through the roof of the van. You get to the office late and have to deal with everything that has been piled on your desk. No time for the gym, and lunch is going to be a bag of peanut M&Ms and a can of Coke. You never see the light of day, except through your office windows. By the time you get home, itʼs dark and the kids are fighting over the Playstation.

You still need to make dinner. Your husband has texted you, heʼs running late and will miss dinner...again.

You pile the kids back in the van and head to a fast food place. Itʼs drive through and the kids donʼt mind. Youʼre famished and get a double cheeseburger, since you skipped lunch, how could it hurt? You get everyone home and get the kids doing their homework. Itʼs nine pm before you know it, and your husband finally gets home. He walks in and just wants to sit in front of the TV, heʼs exhausted. You get the kids bathed and into bed. Itʼs 11pm before you fall into bed, head pounding. You have trouble sleeping, and it seems like by the time you finally drift off, the damn alarm is ringing again!

I do not mean to over-romaticize or idealize the lives of men and women from centuries ago. Theirs was a very different experience, and it was physically and emotional demanding. People got sick then, very sick, and many died premature deaths. But not many suffered from chronic diseases. Our modern lifestyle is much easier in many ways-- we have automated appliances to do our labor, vehicles to transport us, and conveniences our great, great grandparents could only have dreamed of. 

Our modern lifestyle has disrupted many natural and hormonal patterns; such as the circadian rhythm. We no longer use the sun to tell us when to rise and set. And doctors are seeing a deficiency of vitamin D (the sunshine vitamin made by our skin when exposed to sunlight) linked to many diseases. Not coincidentally, lack of vitamin D is one of the causes of endothelial dysfunction.

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More science continues to come in, and we've learned how endothelial dysfunction is linked to slowed cerebral blood flow and inflammation. Some of the modern lifestyle/environmental factors which have been linked to endothelial dysfunction are:

1. Lack of UV rays, low nitric oxide and low Vitamin D

2. Lack of exercise and sedentary living

3. Higher stress and cortisol release

4. Lack of REM sleep and regular circadian rhythms

5. Too much glucose and refined sugar

6. Eating transfats and processed foods

7. Toxins, pesticides and heavy metals in air and food

8. Lower intake of whole foods, fruits and vegetables

And not coincidentally, when countries become industrialized or "westernized", rates of chronic diseases rise. 

Nevertheless it was the Industrial Revolution (with the widespread use of refined vegetable oils, refined cereal grains, and refined sugars)14,65 and the Modern Age (with the advent of the “junk food” industry, generalized physical inactivity, introduction of various pollutants, avoidance of sun exposure, and reduction in sleep time and quality coupled with increased chronic psychological stress)14,38,65,146,152,153,160 that brought about the most disruptive and maladaptive changes, which may have serious pathophysiological consequences.  link

Take care of your endothelium and it will take care of you.

For more information:

http://ccsvi.org/index.php/helping-myself/endothelial-health

Joan

Columbia Researchers Provide New Insight into How the Brain Regulates Its Blood Flow

A group of multi-disciplinary researchers at Columbia University have made an exciting discovery.  They have witnessed how the vascular system regulates blood flow to the brain.
http://engineering.columbia.edu/columbia-engineers-provide-new-insight-how-brain-regulates-its-blood-flow 

The vascular endothelium maintains the lining of all 60,000 miles of our blood vessels, even the vessels inside the brain.  It is the largest secreting organ in the human body.  Neurological researchers had postulated that endothelial cells were not as important in maintaining blood flow inside the brain--that the brain itself was responsible for initiating cerebral blood flow according to neuronal health.  But this theory was wrong.

The brain relies on healthy blood vessels to maintain healthy cerebral blood flow.

The brain was thought to use a different mechanism--and this has lead neurological researchers to focus on the cells surrounding blood vessels in the brain.

According to researcher and professor of biomedical engineering, Elizabeth M.C. Hillman, this supposition has lead to incorrect ideas on brain health.

“Once we realized the importance of endothelial signaling in the regulation of blood flow in the brain,” Hillman adds, “we wondered whether overlooking the vascular endothelium might have led researchers to misinterpret their results.”

Dr. Hillman has spent the past 10 years using advanced medical technology, to study how blood flow is controlled in the brain.  Her research team was comprised of a multi-disciplinary members.  Other lab members who assisted with the study included PhD and MD/PhD students from Columbia Engineering, Neurobiology and Behavior, and Columbia University Medical Center. The group combined their engineering skills with their expertise in neuroscience, biology, and medicine to understand this new aspect of brain physiology.

To tease apart the role of endothelial signaling in the living brain, they had to develop new ways to both image the brain at very high speeds, and also to selectively alter the ability of endothelial cells to propagate signals within intact vessels. The team achieved this through a range of techniques that use light and optics, including imaging using a high-speed camera with synchronized, strobed LED illumination to capture changes in the color, and thus the oxygenation level of flowing blood. Focused laser light was used in combination with a fluorescent dye within the bloodstream to cause oxidative damage to the inner endothelial layer of blood brain arterioles, while leaving the rest of the vessel intact and responsive. The team showed that, after damaging a small section of a vessel using their laser, the vessel no longer dilated beyond the damaged point. When the endothelium of a larger number of vessels was targeted in the same way, the overall blood flow response of the brain to stimulation was significantly decreased.

The researchers damaged the endothelial layer of cells, causing oxidative stress.  After this damage, the blood vessel was no longer able to dilate past the damaged point.  This process restricted blood flow to the neurons.

The damaged endothelium is what initiated lowered blood flow, also known as hypoperfusion.   We see hypoperfusion in MS, Alzheimer's, Parkinson's and dementia.

MS experts have maintained that it is the death of neurons in the brain caused by the unknown disease process we currently call "multiple sclerosis", which leads to a lowered need for cerebral blood flow.   Their assumption has been that the hypoperfusion of the MS brain (which is a scientifically documented fact) is due to MS.  
http://ccsviinms.blogspot.com/2010/08/blood-flow-and-white-matter-lesions.html

But what if this chicken and egg supposition has been wrong?  Have 70 years of EAE postulation and drug development placed the focus on the wrong cells?

Dr. Hillman is urging other researchers to join her in the pursuit of understanding how the vascular endothelium and brain health are connected.  

“Our latest finding gives us a new way of thinking about brain disease—that some conditions assumed to be caused by faulty neurons could actually be problems with faulty blood vessels,” Hillman adds. “This gives us a new target to focus on to explore treatments for a wide range of disorders that have, until now, been thought of as impossible to treat. The brain’s vasculature is a critical partner in normal brain function. We hope that we are slowly getting closer to untangling some of the mysteries of the human brain.”

I share her urgency.  It was seven years ago when I first began looking at the correlation of endothelial dysfunction and neurodegenerative disease.  Blood flow to and from the brain matters.  Understanding how we can reverse endothelial dysfunction and oxidative stress--not only through future drug development---but through present day lifestyle, exercise, nutrition, UV rays, smoking cessation and other means-- is critical in helping those who are suffering from cerebral hypoperfusion found in MS, Parkinson's, Alzheimer's and dementia.

Here's the program I created for Jeff.  I hope it can help you, too!

http://ccsvi.org/index.php/helping-myself/endothelial-health

Time equals brain,

Joan

Full paper A Critical Role for the Vascular Endothelium in Functional Neurovascular Coupling in the Brain  http://jaha.ahajournals.org/content/3/3/e000787.full

The Cure Mentality

Disease organizations have walks, bike rides and a variety of fund raisers to encourage donations to "Find the Cure!"   While these organizations have been spectacularly successful at raising money and in some instances, improving survivability of disease, they have not found cures.  And this fact brings us to the larger question---

Can we actually cure MS?

Cures exist.  But only for some, not all, of human disease.  We love to say, "There's no cure for the common cold!" and we all know there's no cure for dying.   We also know there isn't a cure for cardiovascular disease and stroke---there's only prevention, angioplasty and rehabilitation.  Still, we expect science to figure it out.  We think that researchers will create one pill, one solution, one therapy, one cure. 

I would like to propose that this focus on the cure for MS is keeping us from actual healing.  

How and when did our "cure mentality" begin?    I believe it was during the 1930s and 40s, when penicillin and the vaccine to prevent polio were introduced to the general public.   This was the era when all the big disease organizations were founded, to make sure these promising new scientific explorations continued. 

I researched this period for an essay on the founding neurologist of the MS Society,  Dr. Tracy Putnam.  He was the researcher who showed the vascular connection to MS in an experiment where he occluded the venous sinus of dogs, and created MS lesions and disability.   Yet his vascular theory of MS was tossed aside for "new" science and the autoimmune theory of MS, based on research by a co-creator of the polio vaccine, Dr. Thomas Rivers.  

Why did this happen?  Why didn't researchers follow up on Dr. Putnam's findings?   Because the vascular theory of MS did not produce an immediate "cure."  Patients and advocates expected nothing less. 

Dr. Putnam used newly developed blood thinners to treat MS, and the disease still progressed in some.  Patients and advocates grew weary and looked for new answers.  They turned to the young and successful pioneering scientist, Dr. Rivers.  He created the EAE mouse model of MS, which is still used 70 years later--even though, ironically, it has not produced a cure.  Instead, EAE has been used to create a 20 billion dollar a year industry for pharmaceutical treatments for MS.
link

What if Dr. Putnam was right?  What if MS is a cerebrovascular disease that can be treated, modified and possibly prevented?

Sadly, CCSVI treatment was touted as a potential cure by the press and many patients,  even though Dr. Zamboni and all the pioneers had never claimed this.  We knew it was a treatment and only part of a whole new vascularly healthy lifestyle.  Jeff and I were so discouraged when the New York Times chose to portray us as cure-seekers, and completely misrepresented the research.  
link

Today, we have a similar furor growing over stem cell treatment.  Although stem cell treatments that require immune ablation and chemotherapy have proven harmful, and have not stopped disease progression or brain atrophy in progressive patients.
link


Why do we still look to immunologists and MS specialists for the cure?

We now know that MS is not a genetic disease.  There is not one gene that causes MS. Scientists have located the MHC gene and other loci that raise the potential to develop MS-- but only 4% of people with MS have MHC, with over 200 risk loci identified.  Not exactly a smoking gun. link

And we know MS is not purely autoimmune, like the EAE model used in mice, or we would have a cure by now.  Because copaxone and other drugs have been touted as reversing EAE in mice, but not humans.  link

We do know that MS is affected by environmental factors.  
Proven, scientific links to MS susceptability and progression have been found in low vitamin D levels, low sun/UV exposure, eating processed foods and transfats, cigarette smoking, obesity, stress, lack of exercise and movement, lack of sleep,  and hypoperfusion or slowed blood flow in the brain.

As these Australian researchers have published---prevention may be the best path to healing and disease prevention for MS.
In the face of imperfect and non-curative treatments, understanding the role and mechanisms of action of environmental exposures is highly important as these are potentially preventable.  link

There are things to be done to improve our health.
Could we consider our goal to be prevention, disease cessation and healing, instead of a cure?

What if we took all that energy, money and time we voluntarily give to the disease groups that have continually promised us a cure and reinvested it back into our own lives and our community?

How about using that money to start buying more organic fruits and veggies--and skipping the MS Society hamburger and milkshake fundraiser?   (yes, sadly, this is a real fundraiser.)  link

What if we use our few good hours of daily energy to get physical therapy, take a walk, go to the gym and keep moving our whole bodies?  link

Toss out the cigarettes, and chew on carrot sticks?
link

What if we went outside for 15 minutes, and soaked up some of those nitric oxide releasing UV rays and raised our vitamin D levels naturally?
link

How about meditation instead of frustration?   Deep breathing and deep sleep?
link

Could we heal?  Could we change our disease course?  Science gives us a resounding "yes!!"   As do many medical researchers including Dr. Terry Wahls, Dr. Ashton Embry, Dr. George Jelinek and the late Dr. Roy Swank.

Jeff would tell you these lifestyle changes work.  And his MRI proves he is healing.  His gray matter now looks normal on MRI.  He is not cured--he still has some damage from his first bad flare and neuropathic pain, he still has damage due to "MS".  But it is not getting worse.  His MS is not progressing.  His brain and spine are healing, using venoplasty for CCSVI and the Endothelial Health Program.  link

When we simply sit and wait for a cure and don't change the things we know we can change, we abdicate our power.  We give away our own innate ability for healing.

Wishing everyone who reads this blog hope and true healing,
Please stay in touch with me, and let me know what is helping you to heal.
It's not about blame for the past, it's about real hope for the future.  
We're all in this together--and I remain a cheerleader,

Joan