Heart disease is currently the leading cause of death worldwide — almost 18.6 million people globally died from cardiovascular disease in 2019.
The most common type of heart disease is coronary artery disease, which occurs when plaque builds up inside the blood vessels that supply the heart. When the heart does not receive the blood and oxygen it needs, a person may experience a potentially life-threatening heart attack, clinically called a myocardial infarction.
When heart muscle cells are deprived of blood and oxygen, they can start to die, damaging the heart.
Historically, scientists believed that heart muscle cells, called cardiomyocytes, could not regenerate. This meant any heart muscle cells a person lost during a heart attack they would be unable to regain over time. However, previous research shows heart muscle cells may be able to regenerate.
And now, a research team from Michigan State University presents evidence that a hormone called oxytocin may help stimulate the regeneration of cardiomyocytes. Researchers believe this finding may one day help restore lost heart muscle cells in people who have heart attacks.
This study appears in Frontiers in Cell and Developmental Biology.
Oxytocin is a naturally-occurring hormone produced in the hypothalamus region of the brain.
The hormone is usually associated with functions of the female reproductive system, including childbirth and breastfeeding.
According to Dr. Rigved Tadwalkar, a board-certified cardiologist at Providence Saint John’s Health Center in Santa Monica, CA, oxytocin does not have a medical role outside of obstetrics.
“The most common indications are for the promotion of labor and to control uterine bleeding in the postpartum setting,” he explained to Medical News Today.
Dr. Tadwalkar also pointed out that oxytocin is known as the “love hormone” because it promotes bonding and a positive mood.
“Oxytocin is increased by activities that we often find pleasurable and/ or fulfilling,” he noted. “Typically, these are mind-body activities like meditation, yoga, or sexual intimacy. Also included [are] conversation, cooking, sharing a meal with someone, being charitable, performing acts of kindness, as well as engaging in forms of touch such as hugging, kissing, and massage.”
Past research also shows that oxytocin has a positive impact on the heart, including by helping decrease blood pressure.
Why did researchers decide to look at oxytocin to potentially help with heart muscle cell regeneration?
“Regeneration is a very demanding process energetically and imposes severe restrictions on heart function, so we reasoned there should be some kind of ‘central control’ rather than it being completely autonomous,” study lead author Dr. Aitor Aguirre, assistant professor in the Department of Biomedical Engineering at Michigan State University, explained.
“Our educated guess, based on what is known about central control of other critical processes in the body, was potential neuroendocrine pathways controlled by the brain. With that in mind, we took about 20 or so important neuroendocrine hormones and [checked] out their ability to activate the epicardial stem cells, which participate in heart regeneration. Oxytocin was the top hit,” he said.
Dr. Aguirre and his team used both human tissue in vitro and zebrafish to study how oxytocin helps stimulate stem cells created from the epicardium of the heart — called epicardium-derived progenitor cells — to develop into cardiomyocytes.
“Oxytocin reprograms a population of adult cells in the outer layers of the heart — called the epicardium — and turns them into stem cells,” Dr. Aguirre further explained. “These stem cells migrate into the deeper layers of the injured heart — myocardium — and repair parts of the injury by releasing healing factors and transforming into lost cells — blood vessels, cardiomyocytes, [and] fibroblasts.”
Dr. Aguirre said that after further study, these findings could lead to a treatment to boost a person’s regenerative response:
“Oxytocin and several analogs are already employed in the clinic for other conditions, so it is easy to see it as a potential medication that could be administered to people right after myocardial infarction to boost endogenous regeneration — either as an injection in the bloodstream or maybe a pill using small molecule drugs. [This] could constitute a significant step forward to reduce mortality and morbidity from heart attacks and related conditions where the heart is injured.”
In addition to providing background on oxytocin, Dr. Tadwalkar told MNT that there is absolutely the potential for practical application of this study’s findings in humans.
“We [are] not all the way there yet, but oxytocin, or a similar analog that stimulates its receptor, could conceivably be utilized to regenerate the heart in humans after acute or chronic injury,” he said.
“Unfortunately, oxytocin exists only briefly in the human circulation [with a] short half-life,” cautioned Dr. Tadwalkar. “However, we could take advantage of this beneficial signaling pathway in humans by creating drugs that are higher in potency or with longer half-lives. Since we already use oxytocin clinically, this is not inconceivable.”
Yet Dr. Tadwalkar also emphasized the need to evaluate the potential side effects of an increased dose of oxytocin.
“When oxytocin is boosted naturally, we do not think there are any significant adverse effects,” he explained. “However, several studies have shown that oxytocin could promote dishonesty and fear, the latter due to selective social bonding. When oxytocin is used medically in the obstetric world, there are a variety of systemic side effects. Common ones from a cardiovascular perspective include changes in blood pressure and heart rate, as well as rhythm disturbances.”
MNT also spoke with Dr. Sanjiv Patel, a board-certified interventional cardiologist at MemorialCare Heart & Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA, about this study. He said this was “an exciting start” to a potential way to regenerate heart cells.
“Right now there’s a lot of research going on in terms of reviving [the] damaged part of the heart,” he explained. “A lot of trials in the lab have been successful, but then in the real world when they do clinical trials, it has not been as successful. So this […] has promise, but I think it still has a long way to go still.”
Regarding this research, Dr. Patel said he would like to next see how effectively oxytocin helps regenerate cardiomyocytes.
“How does it regenerate into an effective heart muscle cell?” he asked. “At what point does it stop regenerating? What other factor does it need to increase the mass production of the cells within the heart?”
“We also need to find out under what conditions or what other stimulating factors or chemicals does it need to sustain the change so that it does improve and not just transiently improve and then you’re back to having a problem,” Dr. Patel added.
“That requires a lot of [study]. And after that, obviously, then advance into a hierarchy of mammals to see what happens in their hearts before we get to human levels,” he explained.
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