Changed gene expression after heart surgery extends cardiomyocyte regeneration

While lower vertebrates can repair their adult hearts after a heart attack, mammals — including humans — cannot. The ability to regenerate dead muscle tissue in mammalian hearts disappears just a few days after birth because the heart muscle cells, called cardiomyocytes, exit the cell cycle.

After that, all growth of the heart comes from enlargement of existing cells, not from creation of new muscle cells. In an adult heart attack, heart failure results when the lost cardiomyocytes are replaced by fibrous scar tissue, instead of new muscle cells. This starts a vicious cycle of heart enlargement, loss of pumping function and eventual death.

In 2020, University of Alabama at Birmingham researchers reported that surgery to remove the left ventricle apex of the heart of pigs, one day after birth, somehow extended the replication ability of heart muscle cells. In fact, after such surgery, pigs can completely recover from a heart attack four weeks after birth, without scarring or decline in heart function.

To better understand the underlying gene expression changes in this extended regeneration window, UAB researchers now report nuclear RNA-sequencing of heart muscle cells, using this porcine model. From such knowledge, and much further research yet to come, clinicians may potentially learn how to regenerate adult heart cardiomyocytes after a heart attack.

This study, led by Jianyi “Jay” Zhang, M.D., Ph.D., chair of the UAB Department of Biomedical Engineering, is published as a Circulation research letter.

The researchers compared nuclei from heart tissue of five groups of pigs. Two groups were regeneration models that had left ventricle apical resections, or AR, at postnatal day one, or P1. One of those two groups then had ligation of the left anterior descending coronary artery four weeks after birth, or P28, to induce a myocardial infarction, or MI; this group is called ARP1MIP28. The other group, called ARP1, did not have ligation.

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