So That’s why people with heart disease suffer from sleep problems

Approximately a third of heart disease patients experience difficulties with sleep. A study by the Technical University of Munich (TUM), published in the Science journal, indicates that heart disease interferes with the generation of melatonin, a sleep hormone produced by the pineal gland, with a critical link identified as a ganglion situated in the neck area. The research suggests an unexplored role of ganglia and highlights potential therapies.

It has been recognized for a while that melatonin production can diminish in individuals with heart muscle diseases, such as post-heart attacks. This was typically considered an additional demonstration of how a heart ailment impacts the body systemically.

Now, a group led by Stefan Engelhardt, Professor of Pharmacology and Toxicology at TUM, along with lead author Dr. Karin Ziegler, has discovered a direct cause behind sleep disorders in people suffering from heart diseases.

Stefan Engelhardt explains, “In our work, we show that the problems with the heart muscle affect an organ that would seem at first glance to have no direct link to it.”

The pineal gland, which is responsible for the production of melatonin, is nestled within the brain and, like the heart, is governed by the autonomic nervous system. This system manages involuntary body processes, with the related nerves originating in the ganglia, among other areas. Of particular relevance to the heart and pineal gland is the superior cervical ganglion.

Envisage the ganglion as “an electrical switchbox,” suggests Engelhardt. In a patient with heart disease-related sleep disorders, a fault in one circuit could spark a problem in the circuit breaker that then spreads to another circuit.

The team discovered a buildup of macrophages—cells responsible for eliminating dead cells—in the cervical ganglion of mice suffering from heart disease. The precise mechanisms behind this are yet to be understood.

These macrophages instigate inflammation and scarring in the ganglion, leading to the destruction of nerve cells. In both mice and humans, these nerve cells extend long axons to the pineal gland.

Advanced stages of the disease show a significant decrease in these axons and consequently reduced melatonin levels, disrupting the animals’ day/night rhythm.

Similar physical effects were observed in humans. In a study of nine heart patients’ pineal glands, considerably fewer axons were found compared to a control group. Just like the mice, the superior cervical ganglion in humans with heart disease displayed scarring and was significantly enlarged.

The research team believes that the damage caused by the dead axons could become permanent in the advanced stage of the disease.

“In an early stage we were able to return melatonin production in mice to the original level by using drugs to destroy the macrophages in the superior cervical ganglion. First, this demonstrates the role of the ganglion in this phenomenon. And second, it inspires hope that we can develop drugs to prevent irreparable sleep disturbances in heart disease,” adds Karin Ziegler.

This study not only brings hope for numerous heart patients suffering from sleep disturbances but also encourages a fresh perspective on the role of ganglia.

“New methods such as spatial single cell sequencing make it possible to investigate individual nerve cells much more closely. Our study could prompt researchers to start systematically searching for connections between other diseases in organs linked via ganglia acting as switchboxes and to look at ganglia as starting points in the search for new drugs,” explains Engelhardt.

Engelhardt also emphasizes the potential diagnostic importance of ganglia. Since all the heart patients’ cervical ganglia were significantly enlarged, it is believed this could signal heart failure.

This could easily be examined with a traditional ultrasound device. If subsequent studies confirm these findings, comprehensive heart examinations could be recommended when an enlargement of the ganglion is detected.

Source: 10.1126/science.abn6366

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