When the cardiac muscle is compromised and cells die, it can often lead to death. But researchers at the Weizmann Institute of Science recently discovered a mechanism that could be used to regenerate heart muscle cells. The discovery appeared this week in the Nature Cell Biology journal.
Cardiovascular disease is one of the leading causes of death around the world. One of the reasons for this is the fact that cardiac muscle cells do not regenerate. These cells, known as cardiomyocytes, cease dividing shortly after birth. In the event of a heart attack, these cells die, forming scars that interfere with the normal function of the heart.
The Weizmann Institute’s Professor Eldad Tzahor hypothesized that the reason for the failure of these cells to regenerate had to do with the embryonic development of the heart. In mice, the heart muscle cells continue to divide until about a week after birth, making it possible for a mouse to heal from injury. But this ability exists for only seven days.
The protein ERBB2 plays a role in heart development. ERBB2 is a specialized receptor, a protein that transmits external messages into the cell, and it generally works together with a second, related, receptor by binding a growth factor called Neuregulin 1 (NRG1) to transmit its message. NRG1 is already being tested in clinical studies for treating heart failure.
Researcher Gabriele D’Uva (a postdoctoral fellow on Tzahor’s team) and research student Alla Aharonov noted that cells treated with NRG1 continued to proliferate on the day of birth but that the effect dropped dramatically after seven days, apparently as a result of a drop in the levels of the protein in the cells. “Too little or too much of this protein had a devastating impact on heart function,” Tzahor explained.
The next step was to determine what happens when the protein is activated for a limited time after a heart attack. The team found that they could activate the protein in mice for a short interval following an induced heart attack and obtain nearly complete heart regeneration within several weeks. “The results were amazing,” said Tzahor.
The team is now working on perfecting the method, which could eventually be used to treat humans.