What prevents the heart from recovering?
Kirill Stasevich, "Science and Life"
In all mammals, the heart does not recover: new cells (cardiomyocytes) appear in it only during embryonic development, and the stem cells from which they appear fall asleep immediately after birth. Therefore, after a heart attack, connective tissue in the form of a scar appears on the damaged areas of the heart muscle instead of muscle cells that could contract.
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 a piece of heart muscle in one-day-old mice, the lost volume of tissue was completely restored within three weeks, and two months later the ventricle was already working as if there was no damage. The ability to restore the heart lasted for seven days, the ventricle no longer regenerated in seven-day-old animals.
Regeneration of the area of the heart damaged a day after the birth of the mouse (left) and the formation of scar tissue when damaged at a later age. A picture from the press release of the Center for Regenerative Medicine in Barcelona Young at heart: a novel window to cardiac regeneration - VM.
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.
The results were tried to be reproduced in other research groups, but not everyone succeeded. However, there were those who still managed to see for themselves how the heart muscle is being restored, and among them were Angel Raya and his colleagues from Barcelona Center for Regenerative Medicine. But their goal was not just to see the same result – they wanted to understand why the ability to recover is fading so quickly. Obviously, some changes are taking place in the newborn heart, and it is possible to understand what these changes are only by analyzing the activity of genes in cardiomyocytes.
In the new experiments, the heart was restored only if the damage occurred no later than the first day of life; if the mice were already at least two days old, then a characteristic scar appeared on the heart muscle (that is, the recovery abilities were not enough for a week, but for a much shorter period). One might assume that the genes controlling cell division are switched off in cardiac cells a day after birth.
However, everything turned out to be wrong: an article in Science Advances says that the differences between a "one-day" and a "two-day" heart were in genes related to extracellular matter, or extracellular matrix. This substance is present in all tissues and organs, somewhere there is more of it, somewhere less, but in general it helps the organ to keep its shape, provides mechanical support and helps cells communicate with each other and maintain a working environment around them.
The extracellular matrix includes a variety of biomolecules, the synthesis of which is controlled by certain genes. It turned out that the genes that stimulate the accumulation of intercellular matter in the heart become very active a day after birth, and the heart itself becomes 50% tougher and denser on the second day than the day before.
Moreover, when they tried to turn off the enzyme in the heart of the mice, which is necessary for the formation of the intercellular matrix, the heart muscle continued to recover even three days later. It can be assumed that the heart muscle may well regenerate if it is not hindered by the accumulating intercellular connective tissue. But, of course, if you think about some kind of treatment, then there should be a different way to stimulate the recovery of the heart than a ban on intercellular substance - after all, if there is not enough of it, the heart is also unlikely to be able to work as it should.
However, some experts doubted that it was the restoration that took place here. Let the connective tissue scars on the heart really not form – it is necessary that muscle fibers appear there.
Angel Raya himself claims that muscle tissue did appear in the places of damage to the hearts of mice; but, one way or another, the results will have to be rechecked several times – especially since they relate to such a controversial topic as heart restoration.
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