The immune system promotes spontaneous heart regeneration

However, the inability to proliferate is not true for all animals, and even in mammals, cardiomyocyte proliferation is known, a new study shows.

“Neonatal cardiomyocytes proliferate, and the cardiomyocytes of zebrafish proliferate through adulthood,” says Osaka University Professor Yasushi Fujio.

However, hearts recover well from myocarditis, suggesting adult cardiomyocytes can proliferate in certain conditions. Myocarditis describes inflammation of the heart, usually in response to a viral infection. Many patients will suffer from cardiac dysfunction but recover naturally, largely because of factors activated by the immune response. Fujio’s group prepared mice with myocarditis to investigate this recovery under the assumption that proliferation was not the cause (see table below).

In myocarditis, “we found that STAT3 was activated and that cardiomyocytes could proliferate. But when we knocked-out STAT3, the proliferation was lost,” he continued.

For cells to proliferate, they must enter the cell cycle. Following birth, mammalian cardiomyoctyes exit the cell cycle. Fujio found that in myocarditis, cardiomyoctyes could re-enter the cycle to proliferate and recover heart function.

According to Fujio, in myocarditis “about 1% of cardiomyocytes expressed Aurora B”, an indicator of cells entering the cell cycle, but in myocardial infarction (heart attacks) “only 0.01% of cardiomyocytes expressed Aurora B.”

Fujio’s team also found that the activation of STAT3 and expression of cell cycle markers could be stimulated by the immune protein interleukin 11, suggesting a possible cytokine means to initiate the proliferation.