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Mechanism of hardening of the arteries and potential treatment identified (cam.ac.uk)
77 points by hhs 14 days ago | hide | past | web | favorite | 20 comments

This press release is wildly overselling this research. It's not anywhere near as simple as calcium deposits causing vascular disease. CAC (coronary artery calcification, where this has been most examined) is essentially an inevitable byproduct of the process of atherosclerosis; calcification anywhere is a halmark of necrotized cells. Since atherosclerosis results from necrotic cells (primarily macrophages) which have invaded the vasculature, the extent of coronary artery calcification is a good marker of the extent of atherosclerosis that has occurred and is thus a good predictor of future coronary events.

However, that does not imply that removing coronary calcium will reduce coronary events. In fact, statin therapy by itself actually increases coronary artery calcification.

It turns out that calcified and fibrotic atherosclerotic plaques are not the plaques that rupture and cause thrombosis and myocardial infarction; in fact, the responsible plaques tend to be large, lipid-rich plaques with a thin cap (called thin cap fibroatheromas). Calcium can actually be protective in helping to form robust caps over plaques. There is a lot of work on characterizing cap-Calcium microstructure. Theoretically, removing calcium somehow using drug agents could have an adverse effect.

You seem to be knowledgeable in this matter. I have a question for you. Several years ago, I heard about a theory that these burst-prone "large, lipid-rich plaques" are essentially "band-aids" created for deficiencies in arterial walls. Does that description align with some of the literature you have read on the subject?

Not the op, but I encountered this theory through Dr. Malcolm Kendrick’s blog [1]. I’m only have a basic medical education (studied clinical psychology at a medical university), but I find the theory plausible. Kendrick’s criticism of the currently dominant cholesterol/statin paradigm is definitely worth looking into

1. https://drmalcolmkendrick.org/2016/01/21/what-causes-heart-d...

I have not heard of this particular phrase. It doesn't quite make sense to me off the top of my head; band aid implies they are beneficial, but lipid-rich plaques are not providing structural integrity or protecting against defects. They are harmful sonce they predispose to MI.

It is likely true that they tend to form where there are surface defects; this idea is decades old and a component of Virchow's triad.

>>" Since atherosclerosis results from necrotic cells (primarily macrophages) which have invaded the vasculature"

I would be interested in reading more about this. Do you have any recommendation for a layman?

I'd just look up atherosclerosis on Google to be honest. To state the basic steps in a straightforward fashion: damage of the surface endothelium, entry and oxidation of cholesterol particles and possibly other circulating junk, entrance of macrophages due to immune signaling, necrosis of extravasated macrophages, structural weakness, breaking of the endothelium, thrombosis, infarction, death of whatever was getting the blood flow distally.

There a lot of knobs at each step but that's basically it.

So this seems to be the key paragraph about what starts the hardening.

>Using NMR spectroscopy, the researchers found that when the cells become stressed and die, they release PAR, which binds very strongly to calcium ions. Once released, the PAR starts mopping up calcium into larger droplets which stick onto the components in artery walls that give the artery its elasticity, where they form ordered crystals and solidify, hardening the arteries.

But then they don't discuss it at all - just talk about the potential solutions and discovery etc.

Can anyone elaborate on what this means "that when the cells become stressed and die"? Is this something we have control over? Is it related to stress? Does diet & exercise reduce the incidence of this? Is it inevitable?

Or from another angle "Once released, the PAR starts mopping up calcium into larger droplets which stick onto the components" does this imply that reduction of blood calcium (via exercise etc) reduces the impact of these cell deaths?

"Can anyone elaborate on what this means "that when the cells become stressed and die"? Is this something we have control over? Is it related to stress? Does diet & exercise reduce the incidence of this? Is it inevitable?"

I don't think you're going to find a straightforward answer because "cells becoming stressed and then dying" is typically a good and normal thing. Cells that refuse the cues to self destruct are roughly synonymous with "cancer cells".

When you undergo vigorous exercise, muscle cells (for instance) that cannot keep up with their energy demands undergo apoptosis and make way for other cells that have more efficient energy production. You can enforce natural selection of efficient mitochondria within your own body with vigorous, stressful exercise.

I encourage you to read the excellent book _Power, Sex, Suicide_ by Nick Lane which covers the topics of energy production in the cells and natural selection of mitochondria, etc. A fascinating book.

I would further encourage you to get as much vigorous exercise as you possibly can. There is no reason to pay any attention at all to trivial dietary and supplement optimizations if you aren't undertaking the intervention that covers the first 99% ...

I agree; add to that lots of good sleep, more water than you think you need, and sunlight and you truly have the first 99% covered.

Probably from oxidative stress which can be caused by psychological stress, poor diet, lack of exercise, social stress, smoking, irregular blood glucose, viruses and bacteria, etc. Pretty much the already known risk factors for heart disease.

But more importantly they die from normal processes required for life, so even without risk factors after living long enough everyone would get heart disease. Probably this is why they do not talk much about cells dying and talk about the ways to revert the effect of their death. Aubrey de Grey often talks about this when telling about the SENS foundation.

could be why fasting helps sometimes, because the body will break down and recycle old cells, so they can't do zombie things in the body

The article mentions that minocycline is available as a generic drug. But the article concludes by saying "the technology" has been patented and licensed to Cycle Pharmaceuticals.

Can anyone tell what was patented? I would assume not minocycline, but I've been surprised before about what could be patented.

This struck me as well. The only thing that comes to mind is the way to administer minocycline. But it's obvious that if the treatment works well, other researchers will find other ways to administer this drug, so I don't see a point. They probably follow a standard procedure to recoup the cost of research, but since they choose a generic drug, I wonder if there is a way to monetize it at all.

They can patent minocycline and it's derivatives.

If they made a brand name minocycline, no one would ever use it because it's already generic. However if they can make a derivative that is more efficacious (even if it's only slightly different), they can brand that and sell it under patent for a while.

A number of PARP inhibitors have been recently approved by the FDA as maintenance therapy for ovarian cancer (Olaparib, for example). Since the standard course of treatment for these patients is months to years of treatment, there may be a real-world test of this discovery and the impact of decreased poly ADP ribose on atherosclerosis. Someone should send this article to AZ and Merck so they can follow up with these patients.

Has there been any test to see if humans taking this drug have increased cardiovascular fitness or reduced mortality?

Have there been any tests with animals?

Being a regular crawler on this forum, I do prefer solution and critical thinking inspiration. Round circular discussion and deliberation makes no progression in distributing information. Well, adding a solution ---- Regular fenugreek consumption can reverse the hardening of arteries problem plus various manly things. :)

> The technology has been patented...

How can this ever be allowed?

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