A pill that primes the heart for attack?

Our stem-like cells that mature into heart tissue become inactivated as adults. But a protein that reactivates those cells could help us make new heart muscle after a heart attack.
Written by Janet Fang, Contributor

How do you mend a broken heart? Everyone says time… but new research shows that a small protein can actually boost the formation of new cardiac muscles after a heart attack.

The findings suggest that our resident stem-like cells can be coaxed to become heart muscle cells (or cardiomyocytes) after heart damage. And the implications are huge for cardiovascular regenerative medicine!

Until now, researchers couldn’t pinpoint the appropriate source of cells that give rise to working cardiomyocytes. Heart progenitor cells – those that form various heart tissues – do exist, but they’re not active enough in adults to repair damage.

A few months ago, I wrote about how newborn mice can regenerate their hearts after injury. Harnessing that self-repair in adults, and coaxing our hearts to fix themselves, would be one of the best ways to heal a broken heart. We’re getting closer.

A team led by Paul Riley of University College London found that a small protein called thymosin β4 (Tβ4) – known to encourage regrowth of blood vessels and improve heart function after injury in mice – can activate progenitor cells to become new cardiomyocytes. Nature News reports:

  1. They injected Tβ4 into mice every day for a week.
  2. They stitched together one of their arteries, mimicking a heart attack.
  3. Just 2 days after the ‘injury,’ cells in the mouse hearts were expressing a gene called Wt1. When that gene is expressed by embryonic stem cells, the cells become cardiomyocytes. Wt1, however, is switched off in adults.
  4. A couple of weeks afterwards, those heart cells had moved inward from the heart’s outer layer, clustering around the site of the injury. The cells also took on the size and shape of cardiomyocytes.

The new heart cells (pictured, red) structurally and functionally integrated themselves with the resident muscle (pictured, green). ScienceNOW explains:

They infiltrated the damaged zone left by the simulated heart attack and meshed with other cardiomyocytes physically and electrically, allowing them to beat…

Magnetic resonance imaging scans showed that the hearts of mice that had received thymosin β4 had smaller scars and were able to pump more blood with each contraction than were the hearts of untreated rodents. "Having a resident source of cells that might repair muscle and blood vessels is important," Riley says.

The new cells could probably go on to replace whatever muscle was damaged in a heart attack, but Riley thinks that Tβ4 would become a daily preventative treatment for people with a family history of heart disease.

He envisions an oral tablet that would “prime their heart so that if they had a heart attack the damage could be repaired.”

Deepak Srivastava at the Gladstone Institute of Cardiovascular Disease, who was not involved in this study, is working with RegeneRx Biopharmaceuticals to test Tβ4 injections in humans, according to Nature News. He’s shown that treating mice with Tβ4 within hours of a heart attack helps muscle cells survive the injury. The drug has already passed safety trials, though the new research could change the next phases.

“If we thought about any kind of therapeutic application,” Riley adds, “it’s going to have to be a preemptive strike.”

The study was published in Nature yesterday.

Image: P. Riley / University College London via ScienceNews

This post was originally published on Smartplanet.com

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