Most tissues in the human body are capable of regenerating themselves after injury, but unfortunately, heart muscle cells are not one of them. Now, scientists at the Max Planck Institute have discovered in mice that reprogramming the energy metabolism of these cells allows them to regenerate after a heart attack, which could open up new treatments for this common killer of health.
After a heart attack or other injury, the heart repairs itself with fibrous scar tissue, which helps hold the organ together in the short term, but this part doesn't beat like heart muscle cells. Over time, this can lead to a variety of problems, from further heart attacks to eventual heart failure.
One of the main differences between cardiomyocytes and other tissues is their energy metabolism. Most tissues in the body get energy from sugar through a process called glycolysis, but the heart gets energy from fat, which is called fatty acid oxidation. It turns out that this may be the key to unlocking heart cell regeneration.
Li Xiang and Yuan Xuejun, authors of the study, said: "It is known that animal species capable of regenerating hearts primarily use sugar and glycolysis as fuel for cardiomyocytes. The human heart also primarily uses glycolysis early in development, but then switches to fatty acid oxidation because it produces more energy. As energy production increases after birth, switch, the activity of many genes is changed, and cell division activity is lost. Individual metabolites of energy production also play an important role in the activity of enzymes that regulate gene activity. Therefore, we hope to trigger changes in gene activity by reprogramming energy metabolism, thereby reopening the cell division ability of cardiomyocytes."
To test this idea in mice, the team turned off a gene called Cpt1b, which is key to fatty acid oxidation. Sure enough, the mice's hearts began to grow, with the number of cells nearly doubling over the course of the experiment.
Next, the researchers induced heart attacks in mice lacking Cpt1b and then allowed their hearts to regain oxygen-rich blood. This simulates a patient receiving a stent after a heart attack. After a few weeks, the test mice had significantly less scarring on their heart tissue than the control group, and their heart function was almost back to pre-heart attack levels, the team said.
After careful observation, the researchers identified the mechanism behind this effect. Turning off the gene triggers a cascade that effectively resets heart muscle cells to a less mature state, allowing them to regenerate.
Of course, this is just a proof-of-concept in mice at this stage, but the team says it could be a pathway that could be applied to humans. It should be possible to develop drugs that block the activity of the enzyme produced by Cpt1b, thereby simulating the effects patients demand. However, this is still far from clinical application. Other studies have found success in using stem cells or mRNA to regenerate the heart.
The research was published in the journal Nature.