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Stiff, or hard, arteries impede the flow of nourishing blood to tissues and organs. This can raise the risk of cardiovascular conditions, such as high blood pressure, heart attack, stroke. It can also raise the risk of dementia and other age-related diseases. Now, scientists at the University of Cambridge and King’s College London, both in the United Kingdom, have unraveled the chemical changes that cause arteries to harden.

A recent Cell Reports paper gives a full account of the findings. The study centers around a molecule called PAR, which is short for poly (ADP-ribose). The researchers discovered that PAR could form “dense liquid droplets with calcium ions,” which then crystallize when they combine with the elastic tissues in artery walls.

One site is the intima or the tissue that lines the blood vessel wall. Calcification at this site occurs as part of atherosclerosis.

Before the discovery, scientists thought that PAR only had a role in DNA repair. The new findings reveal that it also promotes calcification in arteries. The researchers also found that the antibiotic minocycline can prevent artery hardening by blocking PAR-triggered calcification.

The treatment, which they tested in cell cultures and rats, does not seem to affect bone. Minocycline is an existing drug with many uses. Doctors typically prescribe it to treat acne.

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Calcification and artery hardening

“Artery hardening happens to everyone as they age,” says Melinda J. Duer, who is a professor in the Department of Chemistry at Cambridge University, “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,” she adds.

The researchers discovered that PAR could form “dense liquid droplets with calcium ions,” which then crystallize when they combine with the elastic tissues in artery walls.

Duer co-led the study with Catherine M. Shanahan, who is a professor of cell signaling at King’s College London. They have been investigating artery calcification for more than 10 years. The British Heart Foundation (BHF) and Cycle Pharmaceuticals, a company in Cambridge, are funding their research.

In their study paper, the authors explain that calcification that hardens arteries commonly occurs at two sites in the blood vessel. One site is the intima or the tissue that lines the blood vessel wall. Calcification at this site occurs as part of atherosclerosis.

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The other site at which artery hardening occurs is in the media, or the tissue inside the blood vessel wall. Hardening of the media usually happens during aging. Shanahan explains that for this particular study, they wanted to find out what triggers the calcification, which takes the form of calcium phosphate crystals.

Duer co-led the study with Catherine M. Shanahan, who is a professor of cell signaling at King’s College London.

They were particularly interested in finding out why the deposits seem to concentrate “around the collagen and elastin, which makes up much of the artery wall.”

In earlier work, the teams had …read more

Source:: Daily times

      

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