A new step to victory over a heart attack

Kirill Stasevich, "Science and Life"

Our life would be much easier if our heart could regenerate. In many fish, amphibians and reptiles, the remaining heart cells can heal any damage. However, in mammals, alas, new cardiomyocytes can appear only during embryonic development – immediately after birth, the stem cells that gave rise to the heart fall asleep. Therefore, after a heart attack, it does not recover, but is scarred: instead of muscle cells that could contract, the damaged area is covered with connective tissue. 

It is believed that this turned out to be the evolutionary price for a more perfect heart: in amphibians and others, heart cells can reverse their development, to the stem stage, and thereby heal damage, but it is the ability to become stem cells that has a bad effect on the actual cardiac functions. In animals, cardiomyocytes work better, but they can't "fall into childhood" later. 

However, in 2011, cardiologist Hesham Sadek and colleagues from the University of Texas suddenly discovered that in young mice, the heart is able to regenerate quickly. After surgical removal of 15% of the ventricular muscle in one-day-old mice, the lost tissue volume was completely restored within three weeks, and two months later the ventricle returned to "normal" functioning. The ability to restore the heart lasted for seven days, the ventricle no longer regenerated in seven-day-old animals. The most curious thing was that regeneration did not occur at the expense of stem cells, but at the expense of ordinary mature heart muscle cells, which, apparently, suddenly remembered how to divide. 

But when researchers from the University of Southern Denmark tried to repeat the experiment, they saw only the usual scarring and no recovery – an article with these upsetting results was published in Stem Cell Reports last spring. Some experts have tried to explain the discrepancy in experimental data by the fact that during regeneration there may be two competing processes, regeneration itself and scarring, and even the slightest differences in experimental conditions can give an advantage to one or the other. In addition, no one saw the cells themselves that restored the heart of mice; the conclusion that mature heart muscle cells, not stem cells, work here was made by indirect signs. 

And yet, apparently, the restoration of the heart by "non-stem" cells is not at all a myth and not an artifact. In a new article published in Nature (Kimura et al., Hypoxia fate mapping identifies cycling cardiomyocytes in the adult heart), the same Hashem Sadek and the staff of the University of Texas Southwestern Medical Center claim that they were able to find exactly the same regenerative cells (Cell that replaces heart muscle found by researchers). They really turned out to be ordinary cardiomyocytes, however, with the preserved ability to divide. Preliminary experiments suggested that such cells would have to multiply with hypoxia, that is, with insufficient oxygen supply. As a result, it was possible to find a small number of cardiomyocytes that resembled the cells of newborns. To detect them, it was necessary to create a genetically modified mouse in which the Hif-1alpha protein (hypoxia-inducible factor 1alpha), necessary for cells in hypoxia, was connected to a protein label that allowed to see a cell with the activated hypoxic Hif-1alpha gene. 

On average, the annual increase in new cells in the heart was 0.62%, which is consistent with earlier estimates. This, of course, is not enough, but now, having the regenerative cells themselves, doctors can try to purposefully shake them, make them divide more actively. Recently, several papers have appeared in which the division genes in cardiac cells were able to be "blindly" awakened with the help of microregulatory RNAs and other epigenetic mechanisms; I would like to hope that now the search and optimization of such methods will go faster – of course, after the same cells can be found in the human heart. 

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30.06.2015