Protein has crucial role in hardening of arteries

Published: 4 November 2019

Scientists have confirmed the role of a key molecule in causing arteries to become blocked, and have identified the biological process behind its involvement.

A protein, known as osteocalcin, causes cells in artery walls, known as vascular smooth muscle cells, to bind with calcium and phosphate in the body and harden into bone-like cells. These cells constrict the arteries, which can contribute to heart disease.

A team of researchers, led by The Roslin Institute, shed light on the pathway behind the process, which could inform the search for treatments.

Currently there are no therapies for the condition, which is managed in severe cases by surgery.

Researchers examined plaques – calcified cell deposits – from artery tissue donated by people who were undergoing surgery. Chemical analysis of the plaques detected the osteocalcin protein close to sites of calcification on artery walls.

Further studies compared cells taken from mice that were unable to generate the osteocalcin protein with those from mice that could form the protein. Lab tests showed that where osteocalcin was absent from cells, hardened deposits were much less likely to form.

Researchers also established that where osteocalcin was absent, there was reduced activity in a key protein known as Wnt, suggesting that Wnt was involved in driving the process.

They also found that the rate at which blood sugars were taken up by hardening cells was key to the process, and may offer a route towards designing drugs to prevent it.

The study is the first to confirm osteocalcin’s role in calcification of blood vessel cells. It was carried out in collaboration with the University of Edinburgh’s Centre for Cardiovascular Science and Columbia University and was published in the Journal of Bone and Mineral Research.

Future studies will examine the role of a protein known as ENPP1, which has previously been shown to prevent calcification, and how this interacts with osteocalcin and other key molecules involved.

Calcification is a significant global health problem and there is a lack of drugs available to manage it. We have uncovered a key mechanism behind the process – it is likely one of many mechanisms involved, but it is an important one, and it may offer routes towards therapeutic intervention.

Dr Vicky MacRae, The Roslin Institute




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