Year of Publication

2020

Degree Name

Master of Science (MS)

Document Type

Master's Thesis

College

Arts and Sciences

Department

Biology

First Advisor

Dr. Julie S. Pendergast

Abstract

Circadian rhythms are approximately 24-hour oscillations of nearly every biological process in the body. The circadian system coordinates these rhythms of physiology and behavior with environmental cycles such as the light-dark cycle. Shift workers, who experience irregular exposure to the light-dark cycle, have chronically disrupted circadian rhythms and increased risk of developing cardiovascular disease, but the mechanisms are unknown. Our studies investigated the effects of light-induced circadian disruption on atherosclerosis in ApolipoproteinE-deficient (ApoE-/-) mice. We found that male ApoE-/- mice housed in constant light for 12 weeks, which results in severe disruption of circadian rhythms or arrhythmicity, developed significantly more atherosclerosis compared to mice in control light-dark conditions, and this increase was attributed to increased atherogenic VLDL/LDL cholesterol fractions. Next, we mimicked circadian disruption experienced by shift workers by housing ApoE-/- mice in chronic jet lag conditions where the light-dark cycle was advanced by 6-hours every week for 12 weeks. In female ApoE-/- mice, we found that that chronic jet lag caused a 70% increase in atherosclerosis and a 23% increase in cholesterol, which was in VLDL/LDL fractions. Together, these data show that light-induced circadian disruption increases atherosclerosis, in part via exacerbated dyslipidemia.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2020.396

Funding Information

This research was supported by National Institutes of Health grants P20 GM103527 (COCVD Investigator to J.S.P.) 08/01/16-07/31/19, DK107851 (to J.S.P) 07/01/16-06/30/19, P30 GM127211 08/01/18-07/31/21, the Gertrude F. Ribble Trust (to J.M.C.) 2018-2019, and the University of Kentucky.

Included in

Biology Commons

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