
Mechanism of hardening of the arteries and potential treatment identified - hhs
https://www.cam.ac.uk/research/news/cause-of-hardening-of-the-arteries-and-potential-treatment-identified
======
et2o
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.

~~~
equalunique
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?

~~~
Henk0
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...](https://drmalcolmkendrick.org/2016/01/21/what-causes-heart-
disease-part-ii/)

------
brational
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?

~~~
rsync
"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% ...

~~~
gehwartzen
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.

------
DoofusOfDeath
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.

~~~
dvfjsdhgfv
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.

------
DrAwdeOccarim
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.

------
ilaksh
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?

------
Maverick4_
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. :)

------
kevin_thibedeau
> The technology has been patented...

How can this ever be allowed?

