Scientists have found that oxytocin, also known as the “love hormone,” may one day be used to aid in the recovery of damaged heart tissue following a cardiac event.

The neurohormone oxytocin is well known for fostering social connections and producing joyful experiences, such as those associated with sex, exercise, or artistic expression. The hormone also controls a variety of other processes, including uterine contractions, breastfeeding, and ejaculation in females and testosterone production, sperm transport, and ejaculation in males.

Now, scientists from Michigan State University have demonstrated that oxytocin has yet another, previously unknown, function in zebrafish and human cell cultures: it encourages stem cells from the heart’s outer layer (epicardium) to migrate into its middle layer (myocardium), where they develop into cardiomyocytes, the muscle cells that cause heart contractions.

One day, this finding might be applied to encourage the regeneration of the human heart following a heart attack.

The findings were reported in the journal Frontiers in Cell and Developmental Biology.

The study’s senior author, Dr. Aitor Aguirre, an assistant professor in the Department of Biomedical Engineering at Michigan State University, said, “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.”

Stem cells can be used to make more cardiomyocytes

After a cardiac attack, cardiomyocetes often disappear in large numbers. They cannot renew themselves since they are highly specialized cells. Epicardium-derived Progenitor Cells (EpiPCs), which can regenerate not only cardiomyocytes but also other types of cardiac cells, have been identified as a subset of cells in the epicardium that can be reprogrammed to become stem-like cells.

“Think of the EpiPCs as the stonemasons that repaired cathedrals in Europe in the Middle Ages,” remarked Aguirre.

Unfortunately, under natural circumstances, the creation of EpiPCs is ineffective for human heart regeneration.

We could learn from zebrafish how to make heart regeneration work better.

Here comes the zebrafish, an animal renowned for its remarkable ability to regenerate organs such as the brain, retina, internal organs, bone, and skin. Since their numerous predators are delighted to eat any organ, including the heart, they don’t experience heart attacks, but zebrafish can regenerate their hearts after losing as much as 25% of it. Cardiomyocyte proliferation and EpiPCs both play a role in this. But how precisely do zebrafish EpiPCs repair the heart? Can we find a “magic bullet” in zebrafish that might enhance the human development of EpiPCs?

Yes, according to the authors, this “magic bullet” seems to be oxytocin.

The authors came to this conclusion after discovering that in zebrafish, the production of the messenger RNA for oxytocin increases up to 20-fold in the brain three days after cryoinjury, or injury brought on by freezing, to the heart. They also demonstrated that this oxytocin gets to the zebrafish epicardium where it attaches to the oxytocin receptor and sets off a chain of events that encourages the growth and development of EpiPCs in nearby cells. In order to replace the missing cardiomyocytes, blood vessels, and other vital heart cells, these new EpiPCs then travel to the zebrafish myocardial.

Similar impact on cultured human tissue

The authors demonstrated that oxytocin had a similar effect on human tissue in vitro. Oxytocin induces cultures of human induced pluripotent stem cells (hIPSCs) to become EpiPCs at up to twice the baseline rate, a far stronger effect than other compounds previously demonstrated to increase EpiPC formation in mice. None of the other 14 neurohormones tested here had this effect. On the other hand, oxytocin receptor genetic knockdown hindered the regenerative activation of human EpiPCs in culture. The authors also demonstrated that the crucial “TGF- signaling pathway,” which is known to control cell proliferation, differentiation, and migration, is the link between oxytocin and the activation of EpiPCs.

“These results show,” as explained by the author, “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.

“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.”

Source: 10.3389/fcell.2022.985298

Image Credit: Getty

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