Date Available
7-29-2020
Year of Publication
2020
Degree Name
Master of Science (MS)
Document Type
Master's Thesis
College
Arts and Sciences
Department/School/Program
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.
Recommended Citation
Chalfant, Jeffrey, "ELUCIDATING THE ROLE OF LIGHT-INDUCED CIRCADIAN DISRUPTION ON ATHEROSCLEROSIS IN APOLIPOPROTEINE-DEFICIENT MICE" (2020). Theses and Dissertations--Biology. 68.
https://uknowledge.uky.edu/biology_etds/68
