Chronic Sleep Fragmentation Plays A Pro-Atherogenic Role In Atherogenesis

Abstract

Abstract Atherosclerosis is a chronic, inflammatory disease characterized by the hardening and narrowing of the small and medium sized arteries caused by the accumulation of fatty plaque lesions. In the USA, approximately 30% of the population reports insufficient sleep, and nearly 70 million people have a diagnosed sleep disorder. Chronic sleep fragmentation (SF) has been shown to have a connection with the development of many common diseases such as, type 2 diabetes, obesity, and cardiovascular disease; however the exact relationship between SF and the progression of atherosclerosis is unknown. Importantly, SF is related to stress conditions, but also has additional unique components that may affect atherogenesis. To examine the effects of SF on atherosclerosis, Apoe−/− mice were placed on a high fat diet (HFD) and sleep was fragmented using a motorized slow moving mechanical sweeper every 2 minutes during the light period each day. After 9 weeks on HFD and SF we found that chronic SF led to increases in plaque formation in HFD fed Apoe−/− mice. The development of atherosclerotic lesions is characterized by the recruitment of leukocytes and myeloid cells into atherosclerotic arteries. To determine if SF alters the immune composition within atherosclerotic aortas, we examined aortic infiltrating leukocyte subpopulations by FACS. We found that the relative proportion of CD45+ cells from SF Apoe−/− aortas was elevated in comparison with control Apoe−/− aortas. We also detected an increased percentage of CD11b+CD115+ macrophages in SF Apoe−/− aortas. Together our data suggests that chronic SF is pro-atherogenic, alters the immune composition of atherosclerosis-prone aortas and facilitates the accumulation of macrophages within the aortic wall.