They discover a key gene in the repair of the heart after a heart attack

They discover a key gene in the repair of the heart after a heart attack

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An international research team led by academics from the University of Bologna (Italy) has identified, in a study published in the journal ‘Nature Cardiovascular Research’, a key gene in the repair of damage to the heart after an attack.

Specifically, the work shows that the inability of heart muscle to regenerate after a heart attack is due, at least in part, to a class of steroid hormones, the glucocorticoids, which push heart muscle cells to mature after birth and, while, block its proliferation.

“Our results show that glucocorticoids act as an important brake on cardiac regenerative capacity: its inhibition showed promising results in the repair of damaged heart tissue. This is a particularly relevant discovery, which in the future could lead to effective treatments to improve heart condition of patients with infarction”, explained the coordinator of the study, Gabriele D’Uva.

The lack of regeneration capacity of heart tissue is a constant from birth as result of the rapid and important changes suffered by the respiratory and vascular system of the newborn to allow the transition from intrauterine to extrauterine life. Specifically, in the neonatal heart, cardiac muscle cells lose the ability to replicate and continue to grow in size.

“Unlike most of the tissues in our body, which are renewed throughout life, heart tissue turnover in adulthood is extremely low, almost inexistent. This is a consequence of both the very low rate of proliferation of heart muscle cells and the absence of a significant population of stem cells in this tissue. Therefore, serious damage to the heart, induced for example by a myocardial infarction, is permanent,” the researchers argued.

To find a way reverse this disability heart regenerative function, the scientists focused on glucocorticoids, a class of hormones that play an important role in development, metabolism, and maintenance of homeostasis, as well as in managing stressful situations.

In preparation for birth, glucocorticoids are known to induce lung maturation. The researchers, however, found that exposure of neonatal heart muscle cells to these hormones induced the cells to lose their proliferative capacity.

Consequently, they analyzed cardiac tissue during the first week of postnatal life and found an increase in the amount of the glucocorticoid receptor (GR), suggesting that glucocorticoid activity increases in the immediate postnatal period.

Given this scenario, the experts hypothesized that glucocorticoids may be responsible for the maturation of cardiac muscle cells, to the detriment of its replicative and regenerative capacity. An idea that has been demonstrated in an animal model through sophisticated molecular biology techniques.

Specifically, deletion of the GR receptor resulted in reduced differentiation of heart muscle cells, that is, their remaining in an immature state, which increased division into new heart cells.

“It has been shown that removal of the glucocorticoid receptor increases the ability of cells to replicate of the heart muscle after a myocardial infarction, promoting a heart regeneration process in a few weeks. Similar results have also been obtained by administering a drug that inhibits the GR receptor already approved for clinical use in humans“, the scientists have settled.

The research team now aims to test possible synergistic effects with other pro-regenerative stimuli to devise most effective strategies for heart regenerationa result that could help millions of patients around the world.

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