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21.01.2025

The link between cardiac disease and sleepless nights

Life Sciences, Kardiovaskuläre Erkrankung

  • Underlying defective melatonin secretion in cardiac patients
  • Early anti-inflammatory intervention prevent fibrotic scarring
  • SCG hypertrophy as biomarker

Ihr Kontakt

Dr. M. Charlotte Hemmer

E-Mail:
chemmer@baypat.de
Telefon:
+49 (0) 89 5480177 - 29
Referenznummer:
B82005

Herausforderung

Cardiac disease is often accompanied by a disruption of the physiologic sleep-wake cycle with a yet unknown mechanism. These disruptions of sleep-wake rhythmicity contribute considerably to the overall disease burden. The sleep-wake cycle is tightly controlled by the daytime-dependent diurnal secretion of melatonin whose secretion in turn is tightly controlled by sympathetic neurons which project from the superior cervical ganglia (SCG). One third of heart disease patients suffer from sleep problems and have low melatonin levels. Its synthesis occurs in the pineal gland and is, together with its secretion, controlled by sympathetic neurons that project from the SCG. The mechanism underlying the altered sleep-wake cycle in cardiac disease has remained elusive and there is no consensus as to the treatment. Interestingly, the SCG harbors heart-innervating neurons in addition to pineal gland-innervating neurons but its role has not been addressed yet.

Innovation

The data presented here revealed severe and likely irreversible immune-mediated destruction of sympathetic axons in pineal glands from humans and mice with cardiac disease . Spatial, single-cell, nuclear, and bulk RNA sequencing traced this defect back to the SCG, which responds to cardiac disease with accumulation of inflammatory macrophages, fibrosis, and selective loss of pineal gland–innervating neurons. Macrophage depletion in the SCG prevented disease-associated denervation of the pineal gland and restored physiological melatonin secretion identifying the mechanism by which diurnal rhythmicity in cardiac disease is disturbed and suggesting a target for therapeutic intervention.

Kommerzielle Möglichkeiten

  • Defective melatonin secretion warrants clinical investigation of melatonin administration for cardiac patients
  • Early anti-inflammatory intervention may prevent fibrotic scarring and ganglionic damage
  • SCG hypertrophy as biomarker for identifying patients most at risk for pineal denervation
  • Plans for a clinical study underway

Entwicklungsstatus

TRL Level 4

References

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