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Switching off MARK4 protein could help patients with heart failure, say University of Cambridge researchers




A discovery that could improve the recovery of people with heart failure has been made by University of Cambridge researchers.

They found that switching off a heart muscle protein called MARK4 may help the blood to pump more efficiently in patients who have had heart attacks.

Switching off a heart protein could help people who have had a heart attack, Cambridge research suggests
Switching off a heart protein could help people who have had a heart attack, Cambridge research suggests

Many drugs that make failing heart muscles contract more strongly have been deemed unsafe, which has created a major gap in heart attack and heart failure treatment.

In the new research funded by the British Heart Foundation, Cambridge scientists found levels of MARK4 were elevated in mouse hearts after a heart attack.

Mice without the protein were 57 per cent better at pumping blood - and this protective effect lasted for the entire four-week follow-up period.

The researchers discovered MARK4 fine-tunes the microtubule network in the heart muscle cell. This network attaches to the machinery that makes heart muscle cells contract and relax.

Increased MARK4 levels led to microtubules being tightly anchored onto the contractile machinery in the heart. This caused more resistance and prevented them from functioning normally. Lower MARK4 levels meant looser anchoring, which made it easier for the heart to contract and relax.

Following a heart attack the speed of contraction was 42 per cent greater in mice without MARK4, while the speed of relaxation was 47 per cent higher than in mice with the protein.

Those without it had functionality close to healthy heart muscle cells, suggesting that drugs to switch off MARK4 could prove very beneficial.

Dr Xuan Li, BHF intermediate research fellow at University of Cambridge BHF Centre of Research Excellence, said: “After years of research we’ve revealed an entirely new and promising way that could help the recovery of failing hearts.

“It’s early days, and we now need to test the longer-term effects of switching off MARK4. But if drugs to do that prove successful, the life-changing benefits could be seen in people with other types of heart disease as well as those who’ve had a heart attack and developed heart failure.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “Heart attacks are a major cause of disability worldwide - people who’ve had a major heart attack are at much greater risk of developing chronic heart failure. There are around 920,000 people living with heart failure in the UK, and we desperately need drugs to drastically improve the heart’s function in these patients.

“These findings are a positive step forward. Further research is needed to refine and test drugs that can target MARK4 before we’ll see them given to people who’ve had a heart attack and develop heart failure.”

This study was also supported by the Isaac Newton Trust, Wellcome, Cancer Research UK and the German Research Foundation.

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