Scientists have discovered that the ‘love hormone’ can actually heal your heart

The study found that oxytocin has heart-healing properties.

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

The neurotransmitter oxytocin is widely recognized to enhance social bonds and produce pleasurable feelings, such as those associated with sex, exercise, or art. However, the hormone has a variety of other functions, such as regulating lactation and uterine contractions in females, regulating ejaculation, transport of sperm, and production of testosterone in males.

Now, scientists from Michigan State University have demonstrated that oxytocin has another, previously unknown, function in zebrafish and human cell culture: it stimulates stem cells from the outer layer of the heart (the epicardium) to migrate into the middle layer (myocardium), where they develop into Cardiomyocytes, which are the muscle cells that cause the heart to contract. 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 Cellular and Developmental Biology.

Dr. said. Aitor Aguirre, associate professor in the Department of Biomedical Engineering at Michigan State University, and senior author of the study.

Stem-like cells can regenerate heart muscle cells

After a heart attack, heart muscle cells often die in large numbers. They cannot renew themselves because they are highly specialized cells. Previous research, however, revealed 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 EpiPCs as the builders who repaired cathedrals in medieval Europe,” Aguirre explained.

Unfortunately, under normal conditions, the production of EpiPCs is ineffective for human heart regeneration.

Zebrafish can teach us how to regenerate hearts more efficiently

Step into the zebrafish: famous for its exceptional ability to regenerate organs, including the brain, retina, internal organs, bones and skin. They don’t suffer heart attacks, but many predators are happy to take a bite of any organ, including the heart – so zebrafish can grow their own heart when it loses up to a quarter of it. This is done in part by proliferation of cardiomyocytes, but also by EpiPCs. But how do EpiPCs from zebrafish efficiently repair the heart? And can we find a ‘magic bullet’ in zebrafish that could artificially enhance the production of EpiPCs in humans?

Yes, and that “magic bullet” appears to be oxytocin, the authors argue.

To reach this conclusion, the authors found that in zebrafish, within three days after cryo-injury – injury due to freezing – of the heart, the messenger’s expression

RNA is a polymeric molecule similar to DNA and is essential in various biological roles in coding, decoding, regulating, and expressing genes. Both are nucleic acids, but unlike DNA, RNA is single-stranded. The RNA strand contains a backbone made up of alternating groups of sugar (ribose) and phosphate. Attached to each sugar is one of four bases – adenine (A), uracil (U), cytosine (C), or guanine (C). There are different types of RNA in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA), and carrier RNA (tRNA).

“data-gt-translate-attributes=”[{” 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. 

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