Most tissues in the body can regenerate themselves after an injury, but unfortunately heart muscle cells aren’t one of them. Now, scientists at the Max Planck Institute have shown in mice that reprogramming the energy metabolism of these cells allows them to regenerate after a heart attack, which could open new therapies for this common killer.
After a heart attack or other injury, the heart patches itself back up with fibrous scar tissue, which helps hold the organ together short-term but doesn’t beat. Over time, this can cause all kinds of problems, from further heart attacks to eventual heart failure.
One of the key differences between heart muscle cells and other tissues is their energy metabolism. Most tissues in the body get their energy from sugars in a process called glycolysis, but the heart gets its energy from fats, which is known as fatty acid oxidation. And this, it turns out, could be key to unlocking heart cell regeneration.
“It is known that animal species capable of regenerating their hearts primarily use sugars and glycolysis as fuel for heart muscle cells,” said Xiang Li and Xuejun Yuan, authors of the study. “The human heart also primarily uses glycolysis in early stages of development, but then switches to fatty acid oxidation because it can produce more energy. With the switch in energy production after birth, the activity of many genes changes and cell division activity is lost. Individual metabolites from energy production also have important functions for the activity of enzymes that regulate gene activities. We therefore hoped to trigger changes in gene activities by reprogramming energy metabolism to turn cell division ability back on in cardiac muscle cells.”
To test the idea in mice, the team switched off a gene called Cpt1b, which is key to fatty acid oxidation. And sure enough, the hearts of these mice began to grow, with cell numbers almost doubling over the course of the experiment.
Next, the researchers triggered heart attacks in mice that lacked Cpt1b, then allowed their hearts to be flushed with oxygen-rich blood again. This models patients that receive a stent after their heart attack. The team says that after a few weeks, scarring of the heart tissue was far reduced in test mice compared to controls, and heart function returned to almost pre-heart attack levels.
On closer inspection, the researchers identified the mechanism behind the effect. Switching off the gene triggers a cascade that effectively resets the cardiac muscle cells to a less mature state, allowing them to regenerate.
Of course, at this stage it’s only been conducted in mice as a proof of concept, but the team says there could be a pathway to human applications. It should be possible to develop drugs that block the activity of the enzyme that Cpt1b produces, which should mimic the effects on demand in patients. However, this would still be a long way off clinical use. Other studies have found success in using stem cells or mRNA to regenerate the heart.
The research was published in the journal Nature.
Source: Max Planck Institute
Really, this is a tremendous breakthrough, I hope it can apply to humans and that we don't abuse it for world records!