Hormone Replacement Therapy & Age Management Medicine: October/November 2022

‘Love Hormone’ Oxytocin Could Help Reverse Damage from Heart Attacks via Cell Regeneration

Sept. 30, 2022 (Study Finds) – EAST LANSING, Mich. — A chemical released during sex could become a new treatment for heart attack patients, new research reveals. Oxytocin, called the “love hormone,” helps heal the organ by boosting production of stem cells, researchers at Michigan State University say.

The findings are based on human tissue grown in the lab and experiments on zebrafish, which have a remarkable ability to repair themselves.

“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,” says senior author Dr. Aitor Aguirre, an assistant professor at the Department of Biomedical Engineering of Michigan State University, in a media release.

Oxytocin stimulates erections and orgasms. In women, it is believed to help sperm reach the egg. The chemical is produced by the hypothalamus in the brain. It is secreted by the pituitary gland. Abnormal amounts have a connection to sex addiction. Oxytocin is also the foundation of many pleasurable feelings, from exercise to lovemaking.

How does oxytocin heal the heart?

Now, the research team reports it also causes stem cells from the heart’s outer layer, or epicardium, to migrate into the middle, known as the myocardium. There they develop into cardiomyocytes, muscle cells that generate heart contractions. The discovery offers hope of promoting regeneration after damaging events like a heart attack. The cells die off in great numbers after a heart attack. Highly specialized cells don’t replenish themselves.

However, previous studies have shown that a subset called EpiPCs (Epicardium-derived Progenitor Cells) can undergo reprogramming, becoming cardiomyocytes or other types of heart cells. “Think of the EpiPCs as the stonemasons that repaired cathedrals in Europe in the Middle Ages,” Aguirre explains.

Production is inefficient for heart regeneration in humans under natural conditions, but the humble zebrafish may hold the key. They are famous for their extraordinary capacity for regenerating organs including the brain, retina, internal organs, bone, and skin.

They don’t suffer heart attacks, but predators are happy to take a bite out of any organ, since zebrafish can regrow their heart when as much as a quarter of it has been lost. This is done by proliferation of cardiomyocytes and EpiPCs. The “magic bullet” appears to be oxytocin.

Repurposing hormone for heart healing ‘is not a long stretch’

In zebrafish, within three days after the heart was exposed to “cryoinjury” by freezing, expression of oxytocin in the brain soared 20-fold. Scans showed the hormone travelled to the epicardium and bound to the oxytocin receptor. This triggered a molecular cascade, stimulating local cells to expand and develop into EpiPCs.

The new cells headed for the zebrafish myocardium to develop into cardiomyocytes, blood vessels, and other important heart cells, to replace those which had been lost. Crucially, the researchers found oxytocin has a similar effect on cultured human tissue. It turned human Induced Pluripotent Stem Cells (hIPSCs) into EpiPCs.

Numbers doubled due to the hormone. None of 14 other brain hormones tested worked. The effect was much stronger than other molecules tried in mice. On the other hand, genetic engineering that knocked out the oxytocin receptor prevented the regenerative activation of human EpiPCs. The link between oxytocin and the stimulation of EpiPCs was identified in a chemical pathway known to regulate the growth, differentiation and migration of cells.

“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 says.

“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.”

The study is published in the journal Frontiers in Cell and Developmental Biology.

South West News Service writer Mark Waghorn contributed to this report.

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