Cause of Hardening of the Arteries- And Potential Treatment- Identified (H)

[appalachiablue]

"Cause of hardening of the arteries -& potential treatment- identified." Research, University of Cambridge, June 11, 2019. EXCERPTS:

A team of UK scientists have identified the mechanism behind hardening of the arteries, and shown in animal studies that a generic medication normally used to treat acne could be an effective treatment for the condition. "Artery hardening happens to everyone as they age...but up until now we haven’t known what controls this process and therefore how to treat it." — Melinda Duer.

The team, led by the University of Cambridge and King’s College London, found that a molecule once thought only to exist inside cells for the purpose of repairing DNA is also responsible for hardening of the arteries, which is associated with dementia, heart disease, high blood pressure and stroke. There is no current treatment for hardening of the arteries, which is caused by build-up of bone-like calcium deposits, stiffening the arteries and restricting blood flow to organs and tissues. Supported by funding from the British Heart Foundation, the researchers found that poly(ADP ribose), or PAR, a molecule normally associated with DNA repair, also drives the bone-like calcification of arteries.

Additionally, using rats with chronic kidney disease, the researchers found that minocycline – a widely-prescribed antibiotic often used to treat acne – could treat hardening of the arteries by preventing the build-up of calcium in the circulatory system. The study, the result of more than a decade of fundamental research, is published in the journal Cell Reports.

“Artery hardening happens to everyone as they age, and is accelerated in patients on dialysis, where even children develop calcified arteries. But up until now we haven’t known what controls this process and therefore how to treat it,” said Professor Melinda Duer from Cambridge’s Department of Chemistry, who co-led the research as part of a long-term collaboration with Professor Cathy Shanahan from King’s College London.



“This hardening, or biomineralisation, is essential for the production of bone, but in arteries it underlies a lot of cardiovascular disease and other diseases associated with ageing like dementia,” said Shanahan. “We wanted to find out what triggers the formation of calcium phosphate crystals, and why it seems to be concentrated around the collagen and elastin which makes up much of the artery wall.”..“I’d been thinking for years that hardening of the arteries was linked to DNA damage, and that DNA damage is a pathway switched on by many agents including smoking and lipids,” said Shanahan. “When this pathway is switched on, it drives the pathologies associated with ageing. If enough damage is present, the arteries will eventually reflect it.”

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. “We never would have predicted that it was caused by PAR,” said Duer. “It was initially an accidental discovery, but we followed it up - and it’s led to a potential therapy.”

Having discovered the links between DNA damage, PAR, bone and artery calcification, the researchers then looked into a way of blocking this pathway through the use of a PARP inhibitor. “We had to find an existing molecule that is cheap and safe, otherwise, it would be decades before we would get a treatment,” said Shanahan...
“Blood vessel calcification is a well-known risk factor for several heart and circulatory diseases, and can lead to high blood pressure and ultimately, a life-threatening heart attack,” said Professor Jeremy Pearson, Associate Medical Director at the British Heart Foundation.

“Now, researchers have shown how calcification of the walls of blood vessels takes place, and how the process differs from normal bone formation. By doing so, they have been able to identify a potential treatment to reduce blood vessel calcification without any adverse effects on bone.
> This type of treatment would benefit many people, and we eagerly await the results of the anticipated clinical trials looking at whether this drug lives up to its early promise.”...

Read More, https://www.cam.ac.uk/research/news/cause-of-hardening-of-the-arteries-and-potential-treatment-identified

- Cell Reports, Poly(ADP-Ribose) Links the DNA Damage Response & Biomineralization. SEE HIGHLIGHTED LINK IN ARTICLE.

[area51]

1. To the Greatest Page with you. n/t

[pandr32]

2. Treatment identified is good news

...and hopefully will be inexpensive.

[appalachiablue]

3. 'Affordable,' yes!

[Guy Whitey Corngood]

4. K&Fuckin' R

[DFW]

5. If the treatment doesn't lead to osteoporosis, it will be a huge breakthrough.

It needs to be effective in removing calcium from arteries but not from bones. That sounds like the major trick, but they must have thought of this as well. As a heart patient myself, I'm looking forward to hearing more about this.

[appalachiablue]

7. Hopefully they've factored that into reasearch, esp. since

bone loss accelerates with age and has the potential for serious health risks. An impt. issue to raise.

[DFW]

8. I really hope so, too. It's not much help if it's only a trade-off.

But I can't imagine that everyone on the research team has overlooked that question.

[appalachiablue]

13. See #9 re 'bone'

[eggplant]

9. From the OP

“Now, researchers have shown how calcification of the walls of blood vessels takes place, and how the process differs from normal bone formation. By doing so, they have been able to identify a potential treatment to reduce blood vessel calcification without any adverse effects on bone.

[appalachiablue]

12. TY, that's impt. to know, and good news.

[alwaysinasnit]

6. K&R Great post, thanks.

[Progressive2020]

10. Science Marches On

Great post. I am heavy and have High Blood Pressure, under control with meds. This study is good news. I will ask my Doctor about possibly using Minocycline to improve cardiovascular health.

[Farmer-Rick]

11. No, no, no, no

I'm allergic to minocycline, gives me hives and itching. Let's hope there is an alternative antibiotic.

[Red Pest]

14. Very interesting paper but...

1. These observations must be confirmed by others and extended.

2. They have yet to do any trials in animals to show that the inhibitors of PARPs will selectively block deposition in the ECM and not in bones.

3. Even if it works in mice or rats, it may not work in humans. There are all sorts of treatments that work in model animals like mice or rats, but fail to work or are unsafe in humans.

[UTUSN]

15. K&R