Cardiology Heart Treatment Concept

Scientists Discover ‘The Love Hormone’ Could Actually Heal Your Heart

Cardiology heart treatment concept

The study revealed that oxytocin has heart-healing properties.

Researchers have found that oxytocin, sometimes called the “love hormone”, may one day help heal damaged hearts after heart attacks.

The neurohormone oxytocin is widely known to promote social bonds and produce pleasurable sensations, 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, and regulating ejaculation, sperm transport, and testosterone production in males.

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

“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, assistant professor in the Department of Biomedical Engineering at Michigan State University and lead author of the study.

Stem cells can replenish cardiomyocytes

After a heart attack, cardiomyocytes often die in large numbers. They cannot reconstitute themselves because they are highly specialized cells. However, previous research has revealed that a subset of epicardial cells can be reprogrammed to become stem cells called epicardial-derived progenitor cells (EpiPCs), which can regenerate not only cardiomyocytes, but also other types of cardiac cells.

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

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

Zebrafish could teach us how to regenerate hearts more efficiently

Enter the zebrafish: famous for its extraordinary ability to regenerate organs, including the brain, retina, internal organs, bones and skin. They don’t suffer from heart attacks, but their many predators are happy to bite into any organ, including the heart. Thus, the zebrafish can regrow its heart when up to a quarter of it has been lost. This is done partly by the proliferation of cardiomyocytes, but also by EpiPCs. But how do zebrafish EpiPCs so effectively repair the heart? And can we find a “quick fix” in zebrafish that could artificially stimulate EpiPC production in humans?

Yes, and that “quick fix” appears to be oxytocin, the authors claim.

To reach this conclusion, the authors found that in zebrafish, within three days of cryoinjury – freezing injury – in the heart, the expression of the messenger

RNA
Ribonucleic acid (RNA) is a polymeric molecule similar to DNA that is essential in various biological roles in gene coding, decoding, regulation and expression. Both are nucleic acids, but unlike DNA, RNA is single-stranded. A strand of RNA has a backbone made up of alternating sugar (ribose) and phosphate groups. Attached to each sugar is one of four bases: adenine (A), uracil (U), cytosine (C) or guanine (G). Different types of RNA exist in the cell: messenger RNA (mRNA), ribosomal RNA (rRNA) and transfer 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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