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‘Cuddle hormone’ heals the heart – Oxytocin can promote heart muscle regeneration after a heart attack

The “cuddle hormone” oxytocin not only strengthens emotional bonds – it also has a healing effect on the heart, as researchers have discovered. As a result, an increased release of oxytocin causes certain cells in the heart wall to convert back into stem cells. These immature stem cells can then form new heart muscle cells and thus help repair damaged parts of the heart – this could provide new approaches to regeneration after a heart attack.

Unlike other muscles, our heart muscle has only limited self-healing powers. If it is damaged by a heart attack or an injury, it is difficult to heal and heart failure often remains. One of the reasons for this is that there are hardly any stem cells in the heart from which new cardiomyocytes can form. However, there are initial indications that cells from the heart wall, the epicardium, can revert to stem cells under certain conditions – and then form new heart muscle cells.

Oxytocin – a complex hormone with multiple effects © public domain

Unexpected effect of the cuddle hormone

Aaron Wasserman and his colleagues from Michigan State University have now discovered a decisive factor for this rebirth: the hormone oxytocin. The impetus for their study came from the observation that, unlike humans, zebrafish have no problem with heart regeneration: If their heart is injured, the heart muscle and its blood vessels grow back quickly. It does this by mass conversion of cells from the heart wall to epicardial-derived progenitor cells (EpiPC).

When the researchers were looking for the impetus for this transformation, they discovered something surprising in the brain of the zebrafish: Large amounts of the “cuddle hormone” oxytocin were released there in response to the heart injury. As a result, the messenger RNA for the production of this hormone increased 20-fold in the zebrafish brain within a short time. However, the hormone did not stay in the brain: it traveled with the blood to the heart, where it triggered a molecular cascade that started the conversion of the epicardial cells into the stem cells.

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Also works on human cell cultures

This raises the question of whether this mechanism can also work in humans. Although a heart attack or heart injury does not cause such an oxytocin surge in us, it is conceivable that the molecular responses to the cuddling hormone are still present in us. To test this, Wassermann and his team cultured human heart wall cells and exposed them to oxytocin and, for comparison, 14 other neurotransmitters.

The surprising result: the human heart cells also responded to the cuddle hormone. While the other messenger substances had little effect, under the influence of oxytocin they increasingly transformed into epicardium-derived progenitor cells. More detailed analyzes revealed that these cells have their own oxytocin receptors, to which the nurturing hormone binds and thus triggers the conversion.

Hope for potential for medicine

“So we showed that oxytocin can activate cardiac repair mechanisms in zebrafish and in human cell cultures,” says senior author Aitor Aguirre. “This response to the oxytocin stimulation is apparently also conserved to some extent in human heart cells.” This could create new possibilities for promoting the regeneration of the heart after a heart attack or injury in humans – for example by administering additional oxytocin.

“Oxytocin has long been used in medicine for other reasons,” explains Aguirre. “So it is by no means utopian to use it in patients who have had a heart attack. Even if this would only lead to a partial regeneration of the heart, the benefits for the patients would be enormous.” Until then, however, the biochemical mechanism and the possible therapy must be investigated in more detail in mammals. (Frontiers in Cell and Developmental Biology, 2022; doi:10.3389/fcell.2022.985298)

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