Excess Cholesterol Provokes PERK Expression in Vascular Smooth Muscle Cells in Atherosclerosis

Atherosclerosis is a condition of localized excesses of cholesterol in blood vessel walls, leading to fatty plaques that narrow and weaken those vessels, ultimately leading to stroke or heart attack. A lot of attention is given to the way in which excess cholesterol induces dysfunction in the macrophage cells responsible for clearing that cholesterol from blood vessel walls, thereby creating a feedback loop in which atherosclerotic plaques grow. Researchers here instead look at the effects of excess cholesterol on smooth muscle cells, and how it draws them into making the problem worse.

"We are trying to identify new pathways that cause atherosclerotic plaque buildup, in particular pathways that involve a certain cell type, called smooth muscle cells. For many years, researchers have been focused on other cell types, like endothelial cells and macrophages, but more recent studies have highlighted a role of smooth muscle cells in plaque formation. We found that if we block a specific protein in smooth muscle cells, we can effectively block the majority of plaque formation from occurring in an animal model."

Using a knockout method, researchers fed genetically modified mice a high fat diet and caused the mice to have high cholesterol levels in their blood to drive atherosclerotic plaque formation. Blocking a specific protein called PERK in these mice resulted in an 80% decrease of atherosclerotic plaque buildup in male mice. "This tells us that blocking PERK in smooth muscle cells is important in plaque formation. Interestingly, this protein is activated in smooth muscle cells by too much cholesterol in the cells. There are a lot of drugs on the market that block the smooth muscle cell pathway. Now that we know this buildup can be blocked by targeting smooth muscle cells, we can use medication that is already available and target this pathway to help patients with atherosclerotic plaque buildup. This is just another way we can block or lower the plaque buildup, especially for those who are unable to prevent atherosclerosis with lifestyle modifications or statins."

Link: https://www.uth.edu/news/story/targeting-a-specific-protein-in-smooth-muscle-cells-may-dramatically-reduce-atherosclerotic-plaque-formation


any news on your cholesterol degrading platform ? You know , i am not getting any younger :)

Posted by: Cuberat at June 23rd, 2022 6:52 PM

@Cuberat: Working on it!

Posted by: Reason at June 23rd, 2022 6:55 PM

I have always had typically low cholesterol (152) yet a scan I had for something else 8 years ago was reported to show I had a small build-up of plaque on a heart valve. What are some possible ways to dissolve or reduce such plaques? I tried taking Life Extension Super K for a year. This product has the largest amount of MK7 which is popular in Japan for reducing plaque. I asked the radiiologist to examine this area a year later when I had a follow-up scan and he said there was no difference. Dissapointing.

Posted by: Dean at July 3rd, 2022 9:41 AM

@Dean - K2 is rather about stopping and reversing calcification. How about aiding K2 with D3, centella asiatica, pycnogenol, GliSODin, niacin, benfotiamine, pantethine, etc? Also, no further plaque build-up is exceptionally excellent result for most people minding the state of the medicine in this regard.

Posted by: SilverSeeker at July 4th, 2022 8:37 AM

no further plaque buildup would be an excellent result for anybody. Unfortunately, all we can get in the big scheme of things is a slow-down. There might be some local reversals but this trend is not our friend.

I tried nattokinase but it was upsetting my stomach, so had to stop it after a month. And no scientifically valid results, anyway :)

Posted by: Cuberat at July 4th, 2022 8:48 AM

@Cuberat - in my humble opinion nattokinase provokes plaques to form spongy structure which gives too high risk of detachment of the plaques and clogging of the vessels. I risk it no more often than 150 mg of nattokinase in one dose, once every two weeks only. Butyric acid on the other side, even in microcapsuled form (which seems to survive gastric acids), is absorbed too early (and metabolised mainly in liver) to aid M1 to M2 conversion. So it's niacin only so far, or correcting microbiota directly, using fucoidan for instance.

Posted by: SilverSeeker at July 4th, 2022 10:04 AM

why do you think nattokinase causes spongy structures? Was there any study ?

Posted by: Cuberat at July 4th, 2022 11:29 AM

@Cuberat educated precaution. There are no human studies on safety of nattokinase for people with advanced atherosclerosis starting taking it alone in such huge doses. Japanese eat it as a natto where 100g of natto is said to contain about 1100 mg of K2. Such mega dose of K2MK7 is known to remove calcification. And while they consume it whole life they don't consume it everyday, do they? What we do differ from their habit, is that we try to use it alone (I do not know if and what dose of K2 it would be taken with) at a late stage of atherosclerosis. Guess what happens when you remove cholesterol and leave calcium plaque in place. So in this case I would wait for safety study than be sorrow. Or make it resemble at least original dietary product, intermittent and with reasonable dose of K2MK7/9/11/[...].

Posted by: SilverSeeker at July 4th, 2022 12:57 PM
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