The effects of fragmented sleep on monocyte and neutrophil distribution within the tissues during atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory disease of large and medium size vessels that progresses across a lifespan and has been extensively linked to insufficient sleep. Poor fragmented sleep quality is strongly associated with all-cause mortality. Accumulating evidence demonstrates the independent effects of atherosclerosis and fragmented sleep on chronic inflammation within multiple tissues. However, there is limited data on the combined effects of sleep fragmentation (SF) and atherosclerosis on the inflammatory environments of multiples tissue. To address this question, we used flow cytometry and qPCR to investigate immune alterations within the peripheral blood, bone marrow, spleen, aorta, small intestine, and brains of female Apoe −/− mice following 12 weeks of high fat diet (HFD) feeding and SF. SF was induced by waking up mice at the day time using a moving bar. Importantly, we used an activity control (AC) group of mice that had a moving bar during nighttime. We found that chronic SF accelerated atherogenesis and induced increased myelopoiesis. Particularly, we detected increases in pro-inflammatory monocytes and neutrophils in the bone marrow, blood, spleen, aortas and small intestines of SF vs AC groups of HFD-fed female Apoe−/− mice. Additionally, we detected increase inflammatory markers in the brains of SF vs the control AC mice. Our data suggests that SF accelerates atherosclerosis and alters the immune composition of multiple tissues including the blood, bone marrow, spleen, small intestine, and aorta of atherosclerosis-prone mice. Furthermore, the increased peripheral monocytosis and neutrophilia may serve as a link to the elevated inflammatory markers in the brains of HFD-fed, female SF Apoe−/− mice. Supported by the American Heart Association Pre-Doctoral Fellowship (20PRE35180156)