@article{3e8771de67c94296bc04687a8fcdac88,
title = "Disruption of circadian rhythm by alternating light-dark cycles aggravates atherosclerosis development in APOE*3-Leiden.CETP mice",
abstract = "Disruption of circadian rhythm by means of shift work has been associated with cardiovascular disease in humans. However, causality and underlying mechanisms have not yet been established. In this study, we exposed hyperlipidemic APOE*3-Leiden.CETP mice to either regular light-dark cycles, weekly 6 hours phase advances or delays, or weekly alternating light-dark cycles (12 hours shifts), as a well-established model for shift work. We found that mice exposed to 15 weeks of alternating light-dark cycles displayed a striking increase in atherosclerosis, with an approximately twofold increase in lesion size and severity, while mice exposed to phase advances and delays showed a milder circadian disruption and no significant effect on atherosclerosis development. We observed a higher lesion macrophage content in mice exposed to alternating light-dark cycles without obvious changes in plasma lipids, suggesting involvement of the immune system. Moreover, while no changes in the number or activation status of circulating monocytes and other immune cells were observed, we identified increased markers for inflammation, oxidative stress, and chemoattraction in the vessel wall. Altogether, this is the first study to show that circadian disruption by shifting light-dark cycles directly aggravates atherosclerosis development.",
keywords = "atherosclerosis, chemokines, circadian rhythm, inflammation, monocytes",
author = "Maaike Schilperoort and {van den Berg}, Rosa and Bosmans, {Laura A.} and {van Os}, {Bram W.} and Doll{\'e}, {Martijn E.T.} and Smits, {Noortje A.M.} and Teun Guichelaar and {van Baarle}, Debbie and Lotte Koemans and Berb{\'e}e, {Jimmy F.P.} and Tom Deboer and Meijer, {Johanna H.} and {de Vries}, {Margreet R.} and Dianne Vreeken and {van Gils}, {Janine M.} and {Willems van Dijk}, Ko and {van Kerkhof}, {Linda W.M.} and Esther Lutgens and Biermasz, {Nienke R.} and Rensen, {Patrick C.N.} and Sander Kooijman",
note = "Funding Information: We thank Lianne van der Wee‐Pals, Trea Streefland, Isabel Mol, and Chris van der Bent (Div. of Endocrinology, Dept. of Medicine, LUMC, Leiden, the Netherlands) for their excellent technical assistance. This work was supported by the Dutch Heart Foundation (2017T016 to SK and 2013T127 to JMG), the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014‐02 ENERGISE to PCNR), and the Rembrandt Institute of Cardiovascular Science (RICS to PCNR and JMG). In addition, this work was supported by the Netherlands Organization for Scientific Research (NWO‐VENI grant 016.136.125 to NRB). MS is supported by a grant from the Board of Directors of Leiden University Medical Center (LUMC). METD, NAMS, TG, DB, and LWMK were supported by a grant from the Strategic Program RIVM (SPR grant S/133800/01) and the Netherlands Ministry of Social Affairs and Employment (KV 110016). Funding Information: We thank Lianne van der Wee-Pals, Trea Streefland, Isabel Mol, and Chris van der Bent (Div. of Endocrinology, Dept. of Medicine, LUMC, Leiden, the Netherlands) for their excellent technical assistance. This work was supported by the Dutch Heart Foundation (2017T016 to SK and 2013T127 to JMG), the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON2014-02 ENERGISE to PCNR), and the Rembrandt Institute of Cardiovascular Science (RICS to PCNR and JMG). In addition, this work was supported by the Netherlands Organization for Scientific Research (NWO-VENI grant 016.136.125 to NRB). MS is supported by a grant from the Board of Directors of Leiden University Medical Center (LUMC). METD, NAMS, TG, DB, and LWMK were supported by a grant from the Strategic Program RIVM (SPR grant S/133800/01) and the Netherlands Ministry of Social Affairs and Employment (KV 110016). Publisher Copyright: {\textcopyright} 2019 The Authors. Journal of Pineal Research published by John Wiley & Sons Ltd",
year = "2020",
month = jan,
day = "1",
doi = "10.1111/jpi.12614",
language = "English (US)",
volume = "68",
journal = "Journal of Pineal Research",
issn = "0742-3098",
publisher = "Wiley-Blackwell",
number = "1",
}