Premium
Circadian Disruption Accelerates Atherosclerosis in ApolipoproteinE ‐deficient Mice
Author(s) -
Pendergast Julie S.,
Chalfant Jeffrey M.,
Howatt Deborah A.,
McGann Eric G.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.572.9
Subject(s) - circadian rhythm , apolipoprotein e , endocrinology , medicine , entrainment (biomusicology) , circadian clock , biology , light effects on circadian rhythm , period (music) , rhythm , physics , disease , acoustics
The circadian system is a network of molecular clocks located throughout the body. These clocks coordinate daily rhythms of behavior and physiology with environmental cycles. Shift work, which chronically disrupts circadian rhythms, increases the risk of developing cardiovascular diseases. The mechanisms by which this happens, however, are largely unknown. Our long‐term goal is to determine how disruption of circadian rhythms causes cardiovascular diseases. Atherosclerosis is the build‐up of plaques in arteries and can lead to myocardial infarction and stroke. In this study, we sought to investigate whether circadian disruption accelerates atherosclerosis in mice. Wild‐type mice do not develop atherosclerotic lesions. Therefore, we studied C57BL/6J ApolipoproteinE ‐deficient (ApoE −/− ) mice because they spontaneously develop atherosclerotic lesions. We first characterized circadian rhythms in ApoE −/− mice. We found that circadian behavioral rhythms, including free‐running periods of activity in constant darkness and constant light, phase angles of entrainment, and phase shifts to light pulses, were similar between wild‐type and ApoE −/− mice. These data show that ApoE −/− mice had no deficits in their circadian behavior rhythms or light responsiveness. Next, we determined if molecular circadian rhythms in tissues were altered in ApoE −/− mice. We analyzed the expression of the circadian timekeeping protein, PERIOD2, in central and peripheral tissues using a luciferase reporter. We found that PERIOD2::LUCIFERASE rhythms in tissues were similar in wild‐type and ApoE −/− mice. We next sought to determine the effect of circadian disruption on atherosclerosis in ApoE −/− mice. Housing mice in constant light profoundly disrupted locomotor activity rhythms in ApoE −/− mice. We also found that atherosclerotic lesion areas were increased in ApoE −/− mice housed in constant light for 3 months compared to those in control 12h light‐12h dark. Together, these data demonstrate that ApoE −/− mice have normal circadian rhythms and chronic circadian disruption accelerates atherosclerosis in ApoE −/− mice. Support or Funding Information This study was funded by National Institutes of Health grant P20GM103527, the Gertude F. Ribble Trust, and the University of Kentucky. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .