Monday, February 27, 2017

"That which cometh out of the mouth"

I have another new theory. No, it's not exactly received medical wisdom. That's what makes it new. :D

In the past few days, I've learned a lot about how atherosclerosis (plaques building up on artery walls) can lead to stroke. I had previously hazily envisioned strokes being caused by a blood clot that just magically appeared in the brain. To the contrary, the blood clot generally comes from somewhere besides the brain. Typically, an atherosclerosis-related stroke-causing blood clot originates in the carotid arteries, right at the point where the carotid artery divides into two arteries, the internal carotid artery and the external carotid artery. Atherosclerotic plaques build up in the vicinity of that "Y"-shaped fork, and rupturing of the plaques triggers formation of a blood clot which then moves up into the head and gets stuck in a smaller artery in the brain.

What causes plaques in the first place? An influential theory is that oxidized LDL cholesterol starts the process of atherosclerosis. (https://academic.oup.com/cardiovascres/article/68/3/353/309912/Oxidized-LDL-a-critical-factor-in-atherogenesis) My questions then are 1) how does the LDL get oxidized and 2) why does it cause plaques right at that carotid junction?

First I looked into what causes the oxidization. A major culprit behind oxidizing of LDL is hypochlorous acid produced by the enzyme myeloperoxidase, which uses hydrogen peroxide (H2O2) and a chloride ion (Cl-) to do so. (https://link.springer.com/article/10.1007/s12170-013-0291-3, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3315351/, http://onlinelibrary.wiley.com/doi/10.1002/biof.5520060208/abstract, http://atvb.ahajournals.org/content/20/7/1716.long?related-urls=yesl20/7/1716)

H2O2 is supposed to be broken down in our bodies by catalase, glutathione peroxidase, and peroxiredoxins. Glutathione peroxidase activity appears to decrease as we age. (https://www.ncbi.nlm.nih.gov/pubmed/18511755) It's not clear exactly why, but our ability to break down H2O2 with our saliva appears to go down by approximately half as we age (https://academic.oup.com/biomedgerontology/article/62/4/361/629357/Age-Related-Changes-in-Salivary-Antioxidant), which means that there is likely going to be some extra H2O2 in our mouths in our later years. Excess H2O2 is harmful to gum tissue (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730038/), and in the gum tissue H2O2 can apparently diffuse in such a way as to end up in the jugular vein (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3745256/).

The jugular vein travels down through the neck, taking all the "used" blood from the head back to the heart. In the neck, the jugular vein is covered by the carotid sheath, which holds the jugular vein next to the carotid artery. My novel hypothesis is this:

Excess aging-related H2O2 from the mouth goes into the jugular vein and then makes its way over to the carotid artery next door, boosting the amount of oxidized LDL in the carotid artery just before it hits the "Y"-shaped fork, where the oxidized LDL hits the sides of the branching arteries and starts the process of forming atherosclerotic plaques. 

I think the weakest link in my theory is that I can't find a lot of clear proof that H2O2 can migrate from a vein into a neighboring artery; however, it does seem to be generally accepted that H2O2 diffuses through tissues:

It is now widely accepted that this low molecular weight molecule is utilized in metabolic regulation in ways similar to diffusible gases such as NO, CO, or H2S. Even more so, H2O2 is recognized as being in the forefront of transcription-independent signals, in one line with Ca2+ and ATP. H2O2 diffuses through tissues to initiate immediate cellular effects, such as cell shape changes, the formation of functional actomyosin structures, and the recruitment of immune cells.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3979367/

I suppose this will have to suffice for now. It's time to go eat dinner with my family...a nice, low-fat, high-soluble-fiber, and antioxidant-full meal.

(I almost forgot to explain the title of my post. In Matthew 15:11, it is recorded that Jesus said, "Not that which goeth into the mouth defileth a man; but that which cometh out of the mouth, this defileth a man." My research above points to oxidizing substances from the mouth contributing to the formation of atherosclerotic plaques in the carotid arteries.)

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