Blocking circadian clock to treat heart attacks!

Blocking circadian clock to treat heart attacks!

A leading cause of death worldwide, heart attacks trigger inflammatory responses that cause a scar to form in the heart. Over time, that damage eventually leads to incurable heart failure.

Administered within hours of an attack, the potential drug would prevent scarring. It would also eliminate the need for patients to take possibly debilitating heart medication for the rest of their lives.

The circadian "clock" is found in virtually all cells of the body. It consists of genes and proteins that interact during 24-hour day and night cycles to regulate key functions such as heart rate and blood pressure.

In the heart, that clock mechanism controls healthy cardiovascular physiology as well as how the heart responds to damage and undergoes repair.

The researchers' new paper was published in Nature Communications Biology. The researchers used a drug called SR9009, which targets a key component of the cellular clock mechanism. The medication disrupts expression of genes that trigger adverse immune responses after a heart attack.

In experiments with mice, the treatment reduced production of a cellular sensor called the NLRP3 inflammasome that contributes to scarring. The researchers showed for the first time that giving this treatment after a heart attack along with conventional therapy such as reperfusion led to less inflammation and better cardiac repair.

That allowed healing almost as though no heart attack had happened, said the senior author. "No scar, no heart damage, no heart failure - people can survive heart attacks because the heart won't even be damaged. 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."

The discovery might ultimately help in other heart therapies involving early adverse inflammatory response such as organ transplant or valve replacement, the author added. More generally, it may also help with profound adverse inflammatory responses, such as treatment of traumatic brain injury, strokes or severe burns, the author said.

"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," said the senior author. "Circadian medicine is truly a promising new field that will lead to longer, healthier lives."