Myeloid Mayhem: How sleep alters the myeloid compartment and promotes plaque rupture in atherosclerosis

Abstract Adequate sleep is vital for overall health; however, today’s fast-paced society often neglects the importance of sleep. Poor sleep quality is tightly correlated with atherosclerosis and increased risk of mortality due to a cardiovascular event. Evidence demonstrates neutrophilia and monocytosis following chronic sleep fragmentation, but their effects on aortic inflammation and atherosclerotic plaque stability are not well understood. We found that chronic sleep fragmentation accelerated atherogenesis and decreased plaque stability in plaques of high fat diet (HFD) fed female apoliportein E-deficient (Apoe−/−) mice. Sleep fragmentation increased populations of pro-inflammatory monocytes and neutrophils in the bone marrow, blood, spleen, and small intestines of HFD fed female Apoe−/− mice. Additionally, sleep fragmentation increased gut permeability and circulating LPS in HFD fed female Apoe−/− mice. We also observed increased percentage of neutrophils in carotid arteries of sleep fragmented Apoe−/− mice. Importantly, these plaques exhibited increased necrotic areas, altered composition of extracellular matrix, and reduced production of stabilizing collagen. Taken together, our data indicates that sleep fragmentation accelerates plaque formation, and destabilizes atherosclerotic plaques by altering the local and systemic immune landscape. Sleep fragmentation contributes to systemic inflammation and likely activates the innate immune response at least partially, through the increase in circulating LPS mediated by inflammation in small intestines.