Scientists Discover The “Love Hormone” Can Actually Heal Your Heart

Researchers have found that oxytocin, also known as the “love hormone,” may one day help heal damaged hearts after a heart attack.

The neurohormone oxytocin is widely recognized for promoting social connections and producing pleasurable feelings, such as those associated with sex, exercise, or art. However, the hormone has a number of other functions, such as regulating breastfeeding and uterine contractions in women, and regulating ejaculation, sperm transport and testosterone production in men.

Now, scientists of Michigan State University have shown that oxytocin has another previously unknown function in zebrafish and human cell cultures: it stimulates stem cells from the outer layer of the heart (epicardium) to migrate to the middle layer (myocardium), where they develop into cardiomyocytes, the muscle cells that cause heart contractions. This finding could one day be used to promote regeneration of the human heart after a heart attack. The researchers’ findings were recently published in the journal Frontiers in Cell and Developmental Biology.

“Here we show that oxytocin, a neuropeptide also known as the love hormone, is able to activate cardiac repair mechanisms in injured hearts in zebrafish and human cell cultures, opening the door to potential new therapies for cardiac regeneration in humans,” said Dr. . Aitor Aguirre, an assistant professor in the Department of Biomedical Engineering at Michigan State University, and the study’s senior author.

Stem-like cells can replenish cardiomyocytes

After a heart attack, heart muscle cells often die in large numbers. They cannot replenish themselves because they are highly specialized cells. However, previous research has shown that a subset of cells in the epicardium can be reprogrammed to become stem-like cells known as Epicardium-derived Progenitor Cells (EpiPCs), which can regenerate not only cardiomyocytes, but other types of heart cells as well.

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

Unfortunately, under natural conditions, the production of EpiPCs is inefficient for the regeneration of the human heart.

Zebrafish can teach us how to regenerate hearts more efficiently

Enter the Zebrafish: Famous for their extraordinary ability to regenerate organs, including the brain, retina, internal organs, bones and skin. They don’t have heart attacks, but the many predators like to take a bite out of every organ, including the heart – so zebrafish can grow their hearts when as much as a quarter of it is lost. This occurs partly through proliferation of cardiomyocytes, but also through EpiPCs. But how do zebrafish EpiPCs repair the heart so efficiently? And can we find a ‘magic bullet’ in zebrafish that can artificially stimulate the production of EpiPCs in humans?

Yes, and this “magic bullet” turns out to be oxytocin, the authors argue.

To reach this conclusion, the authors found that in zebrafish, within three days of cryo-injury – injury from frostbite – to the heart, the expression of the messenger[{” attribute=””>RNA for oxytocin increases up to 20-fold in the brain. They further showed that this oxytocin then travels to the zebrafish epicardium and binds to the oxytocin receptor, triggering a molecular cascade that stimulates local cells to expand and develop into EpiPCs. These new EpiPCs then migrate to the zebrafish myocardium to develop into cardiomyocytes, blood vessels, and other important heart cells, to replace those which had been lost.

A similar effect on human tissue cultures

Crucially, the authors showed that oxytocin has a similar effect on human tissue in vitro. Oxytocin – but none of 14 other neurohormones tested here – stimulates cultures of human Induced Pluripotent Stem Cells (hIPSCs) to become EpiPCs, at up to twice the basal rate: a much stronger effect than other molecules previously shown to stimulate EpiPC production in mice. Conversely, genetic knock-down of the oxytocin receptor prevented the regenerative activation of human EpiPCs in culture. The authors also showed that the link between oxytocin and the stimulation of EpiPCs is the important ‘TGF-β signaling pathway’, known to regulate the growth, differentiation, and migration of cells.

Aguirre said: “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.”

Aguirre concluded: “Next, we need to look at oxytocin in humans after cardiac injury. Oxytocin itself is short-lived in 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.”

Reference: “Oxytocin promotes epicardial cell activation and heart regeneration after cardiac injury” by Aaron H. Wasserman, Amanda R. Huang, Yonatan R. Lewis-Israeli, McKenna D. Dooley, Allison L. Mitchell, Manigandan Venkatesan and Aitor Aguirre, 30 September 2022, Frontiers in Cell and Developmental Biology.
DOI: 10.3389/fcell.2022.985298

The study was funded by the National Institutes of Health, the American Heart Association, and the Spectrum-MSU Foundation.