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Drug that targets body clock may prevent heart attack damage

A preclinical study in mice has tested a new method that could prevent the scarring that occurs after a heart attack and thus prevent heart failure. The researchers have used a drug to target aspects of the body clock that trigger harmful immune responses.
anatomical model of human heart
Researchers are developing a treatment that may promote heart muscle healing after a heart attack and prevent associated heart failure.

According to the Centers for Disease Control and Prevention (CDC), someone in the United States experiences a heart attack every 40 seconds.

In this medical emergency, the blood flow to the heart becomes obstructed, stopping the organ from functioning normally and damaging some of its muscle tissue.

After a heart attack, as the heart tissue begins to heal, scar tissue forms and is unable to contract and relax as well as healthy tissue.

With time, this may lead to heart failure, in which the heart becomes unable to pump blood effectively.

While various treatments can help individuals with heart failure manage their condition, there is no cure that can reverse it. But what if doctors were able to prevent scar tissue from forming after a heart attack and thus make heart failure less likely?

This is precisely what a team of researchers from the University of Guelph, in Ontario, Canada, are working toward. In a preclinical study in mouse models, the research team has tested a new method that aims to prevent the formation of scar tissue in the heart.

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In a study paper that appeared today, in Nature Communications Biology, Prof. Tami Martino and Cristine Reitz, a doctoral researcher at Guelph, explain that they have used a research drug called SR9009 to target aspects of the circadian clock, or body clock.

This "clock" regulates the body's automatic functions, such as breathing, as well as other more subtle mechanisms, including some immune system responses. When it comes to heart health, circadian mechanisms control, among other things, the ways in which this organ responds to damage and repairs itself.

In the current research, Prof. Martino and Reitz used SR9009 to block the expression of certain genes that play a role in triggering harmful immune responses that eventually lead to the formation of scar tissue following a heart attack.

To test this approach, the investigators administered the drug to mice and found that SR9009 helped reduce NLRP3 inflammasome production. This is an intracellular sensor that reacts to danger signals after a heart attack and contributes to scarring.

The researchers' experiments showed that, when administered within hours of a heart attack alongside conventional medication, the drug led to lower inflammation and better repair of the heart muscle. In fact, the team notes, the approach almost made it look as if a heart attack had not even occurred.

This approach, the investigators observe, might, in the future, allow individuals to avoid having to take heart medication for the rest of their lives.

"No scar, no heart damage, no heart failure — people can survive heart attacks because the heart won't even be damaged," says Prof. Martino.

"We were amazed to see how quickly it worked and how effective it was at curing heart attacks and preventing heart failure in our mouse models of the disease."

Prof. Tami Martino

Besides being a promising therapy for heart attack, the new method, the researchers argue, could help mitigate harmful inflammation in other medical scenarios, as in the case of organ transplants, traumatic brain injury, or stroke.

"What we are discovering is that the circadian clock mechanism is important, not just for heart health but also for how to heal from heart disease," says Prof Martino.

"Circadian medicine is truly a promising new field that will lead to longer, healthier lives," she adds.

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