Heart Disease Directly Impacts Sleep Hormone Production

Researchers at the Technical University of Munich show – for the first time – that cardiac conditions directly impact the pineal gland’s production of the sleep-related hormone melatonin. The study, published in Science, furthers our understanding as to why patients with heart disease experience sleep issues.

Heart disease and lack of sleep – what’s the link?

An estimated 44% of heart disease patients experience sleep issues. Reduced melatonin levels have been detected in such patients, but the new study – led by Professor Stefan Engelhardt –  is the first to demonstrate a direct causative link between cardiac conditions and sleep disturbances. The link is a ganglion found in the neck region.

Melatonin, a hormone that regulates the body’s sleep–wake timing and other physiological processes such as blood pressure, is produced by the pineal gland deep in the center of the brain. “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,” Engelhardt says.

The research team analyzed pineal glands from mice and humans with cardiac disease, where they found “substantial” denervation compared to control groups. Using a collection of sequencing tools, including single-cell, nuclear and bulk RNA sequencing, they discovered that denervation was occurring because of the cardiac disease, which caused macrophage accumulation in the superior  cervical ganglion (SCG).

Macrophages are a type of white blood cell that are important for the detection and phagocytosis of damaged or dead cells. Engelhardt and colleagues show that, in the SCG, the macrophages trigger inflammation, scarring and destruction of the nerve cells, the axons of which lead to the pineal gland in both mice and humans. In the study, the mouse models were found to have lower melatonin levels and their sleep–wake cycle was disrupted.

“To get a clear sense of our results, imagine the ganglion as an electrical switchbox. In a patient suffering from sleep disturbances following a heart disease, you can think of a problem with one wire causing a fire to break out in the switchbox and then spreading to another wire,” says Stefan Engelhart.

Hope that drugs could prevent sleep disturbances

In models of early-stage cardiac disease, the research team could restore melatonin production by reducing the number of macrophages in the SCG via pharmacological means. “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,” says Dr. Karin Ziegler, the study’s first author.

For Engelhardt, the work provides new motivation to look closely at the ganglia when diagnosing health conditions: “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,” he concludes.

This article is a rework of a press release issued by the Technical University of Munich. Material has been edited for length and content.

Reference: Ziegler KA, Ahles A, Dueck A, et al. Immune-mediated denervation of the pineal gland underlies sleep disturbance in cardiac disease. Science. 2023;381(6655):285-290. doi:10.1126/science.abn6366