The research discovered that oxytocin had heart-healing properties.
Researchers have discovered that oxytocin, typically often known as the “love hormone,” might sooner or later assist heal broken hearts after a coronary heart assault.
The neurohormone oxytocin is well known for fostering social connections and producing pleasurable emotions, reminiscent of these related to intercourse, train, or artwork. Nevertheless, the hormone has quite a lot of different capabilities, such because the regulation of lactation and uterine contractions in females, and the regulation of ejaculation, sperm transport, and testosterone manufacturing in males.
Now, scientists from Michigan State College have demonstrated that oxytocin has yet one more, beforehand unknown, perform in zebrafish and human cell cultures: it stimulates stem cells from the guts’s outer layer (epicardium) emigrate into its center layer (myocardium), the place they grow to be cardiomyocytes, the muscle cells that trigger coronary heart contractions. This discovering may sooner or later be used to advertise the regeneration of the human coronary heart after a coronary heart assault. The researchers’ findings had been not too long ago printed within the journal Frontiers in Cell and Developmental Biology.
“Right here we present that oxytocin, a neuropeptide also referred to as the love hormone, is able to activating coronary heart restore mechanisms in injured hearts in zebrafish and human cell cultures, opening the door to potential new therapies for coronary heart regeneration in people,” stated Dr. Aitor Aguirre, an assistant professor on the Division of Biomedical Engineering of Michigan State College, and the research’s senior writer.
Stem-like cells can replenish cardiomyocytes
After a coronary heart assault, cardiomyocytes typically die off in massive numbers. They can not replenish themselves since they’re extremely specialised cells. Earlier analysis has revealed, nonetheless, {that a} subset of cells within the epicardium could also be reprogrammed to turn out to be stem-like cells often known as Epicardium-derived Progenitor Cells (EpiPCs), which may regenerate not solely cardiomyocytes but in addition other forms of coronary heart cells.
“Consider the EpiPCs because the stonemasons that repaired cathedrals in Europe within the Center Ages,” defined Aguirre.
Sadly, beneath pure situations, the manufacturing of EpiPCs is inefficient for human coronary heart regeneration.
Zebrafish may train us the best way to regenerate hearts extra effectively
Enter the zebrafish: well-known for his or her extraordinary capability for regenerating organs, together with the mind, retina, inside organs, bone, and pores and skin. They don’t endure coronary heart assaults, however its many predators are completely happy to take a chunk out of any organ, together with the guts – so zebrafish can regrow their coronary heart when as a lot as 1 / 4 of it has been misplaced. That is performed partly by proliferation of cardiomyocytes, but in addition by EpiPCs. However how do the EpiPCs of zebrafish restore the guts so effectively? And might we discover a ‘magic bullet’ in zebrafish that would artificially enhance the manufacturing of EpiPCs in people?
Sure, and this ‘magic bullet’ seems to be oxytocin, argue the authors.
To succeed in this conclusion, the authors discovered that in zebrafish, inside three days after cryoinjury – harm as a consequence of freezing – to the guts, the expression of the messenger 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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