Bidirectional Crosstalk Between Sleep and Pulmonary Arterial Hypertension

Area of Science:

• Cardiopulmonary Medicine
• Sleep Science
• Vascular Biology

Background:

• Pulmonary Arterial Hypertension (PAH) involves vascular remodeling and is linked to poor sleep quality.
• The impact of poor sleep on PAH progression, hemodynamics, and symptoms is not well understood.

Purpose of the Study:

• To investigate the effects of sleep disturbances on PAH progression using mouse models.
• To explore the molecular mechanisms linking poor sleep to pulmonary vascular remodeling in PAH.
• To determine if PAH itself affects sleep quality in mice.

Main Methods:

• Utilized mouse models with sleep fragmentation and chronic jet lag to study PAH.
• Analyzed clock gene expression in human pulmonary artery smooth muscle cells (PASMCs) from PAH and non-PAH patients.
• Employed RNA-sequencing, immunostaining, proliferation assays, and EEG/EMG recordings.

Main Results:

• Poor sleep exacerbated right ventricular dysfunction, pulmonary vascular remodeling, and PAH severity.
• Sleep disturbances induced lung inflammation, affecting the pulmonary vascular molecular clock and promoting PASMC hyperproliferation and migration.
• PAH was found to cause poor sleep quality in mice; interventions like melatonin and clodronate improved PAH outcomes.

Conclusions:

• PAH induces poor sleep, creating a self-amplifying cycle that exacerbates the disease through inflammation and increased PASMC proliferation.
• Targeting both sleep disturbances and inflammation may represent a novel therapeutic strategy for PAH patients.
• This study highlights the bidirectional relationship between sleep and PAH, suggesting combined treatments could improve clinical outcomes.