Light-Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes.

Area of Science:

• Cardiovascular Research
• Chronobiology
• Molecular Biology

Background:

• Epidemiological studies link shift work to increased atherosclerosis and vascular events.
• Mechanisms underlying shift work's vascular impact are poorly understood.
• Mouse models require adjusted light stimuli to accurately represent human circadian system sensitivity.

Purpose of the Study:

• To investigate the impact of shift work on atherosclerosis progression in a mouse model.
• To establish a relevant mouse model for studying the vascular consequences of rotating shift work.

Main Methods:

• Low-density lipoprotein receptor knockout mice were exposed to simulated day shift or rotating shift work light-dark patterns.
• Rotating shift work involved 11 weeks of reversed light-dark cycles for 4 days/week.
• Light stimuli were calibrated monochromatic green light at 4 µW/cm² to mimic human circadian sensitivity.

Main Results:

• Rotating shift work disrupted the molecular clock in foam cells, increasing endoplasmic reticulum stress and apoptosis.
• Atherosclerotic lesions in rotating shift workers were larger.
• These lesions showed reduced prostabilizing fibrillar collagen and increased necrotic areas.

Conclusions:

• Rotating shift work in mice leads to larger, more vulnerable atherosclerotic plaques.
• This mouse model is valuable for mechanistic and interventional studies on the vascular effects of rotating shift work.