The neurohormone oxytocin – often referred to as the “love hormone” – is known for promoting social bonds and giving rise to pleasurable feelings after activities including exercise, sex, or even art-viewing. However, this hormone has many other functions, such as the regulation of lactation and uterine contractions in females, as well as the regulation of testosterone production, ejaculation, and sperm transport in males.
Now, a team of scientists from Michigan State University (MSU) has found that, in both zebrafish and human cell cultures, this hormone has yet another, surprising function: it stimulates cells from the epicardium (the heart’s outer layer) to migrate into the myocardium (the inner layer), where they develop into cardiomyocytes, a type of muscle cells that generate heart contractions. In the future, these findings could be used to promote the regeneration of the human heart after heart attacks.
“Here we show that oxytocin, a neuropeptide also known as the love hormone, is capable of activating heart repair mechanisms in injured hearts in zebrafish and human cell cultures, opening the door to potential new therapies for heart regeneration in humans,” said study senior author Aitor Aguirre, an assistant professor of Biomedical Engineering at MSU.
After a heart attack, cardiomyocytes usually die off in great numbers and, since they are highly specialized cells, they cannot replenish themselves. However, a subset of cells in the epicardium can turn into stem-like cells called Epicardium-derived Progenitor Cells (EpiPCs) can help regenerate not only cardiomyocytes, but also other types of heart cells. “Think of the EpiPCs as the stonemasons that repaired cathedrals in Europe in the Middle Ages,” Professor Aguirre said.
While under natural conditions, the production of EpiPCs is inefficient for heart regeneration in humans, in zebrafish – a species of animal famous for its extraordinary capacity of regenerating organs – these cells can easily repair damaged hearts. According to the scientists, within three days after cryoinjury (injury due to freezing), the expression of the messenger RNA for oxytocin increases up to 20-fold in their brain. This oxytocin then travels to their epicardium and binds to the oxytocin receptor – a molecular cascade which stimulates local cells to expand and develop into EpiPCs that migrate to the myocardium to develop into cardiomyocytes, blood vessels, and other crucial heart cells.
Importantly, the scientists also showed that oxytocin has a similar effect on human tissue in vitro, by stimulating cultures of human Induced Pluripotent Stem Cells (hIPSCs) to become EpiPCs. “These results show that it is likely that the stimulation by oxytocin of EpiPC production is evolutionary conserved in humans to a significant extent. Oxytocin is widely used in the clinic for other reasons, so repurposing for patients after heart damage is not a long stretch of the imagination. Even if heart regeneration is only partial, the benefits for patients could be enormous,” Professor Aguirre explained.
“Next, we need to look at oxytocin in humans after cardiac injury. Oxytocin itself is short-lived in the circulation, so its effects in humans might be hindered by that. Drugs specifically designed with a longer half-life or more potency might be useful in this setting. Overall, pre-clinical trials in animals and clinical trials in humans are necessary to move forward,” he concluded.
The study is published in the journal Frontiers in Cell and Developmental Biology.
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