Leiden University Scholarly Publications

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In het Panhuis, W. (2023)

Atherosclerotic cardiovascular disease: interplay between sex, age, and circadian rhythms

Doctoral Thesis
Cardiovascular diseases (CVD) are the leading mortality cause. Its largest underlying issue is atherosclerosis: arterial narrowing due to the buildup of cholesterol, lipids, and immune cells. High blood pressure and cholesterol levels are well-known risk factors. Despite the effectiveness of currently-available medication to improve these factors, a considerable residual risk remains, indicating the importance of other risk factors, such as age and sex. Women have a lower risk of developing CVD than men at a young age, which reverses at older age. CVD are also more common among night shift workers. The research described in this thesis used mouse models to provide new insight in the interplay between sex, age, and disturbances in day and night rhythms in atherosclerosis development, and emphasize the importance of including both men and women in scientific studies. Brown fat is one of the tissues adversely affected by disturbances in day and night rhythms and aging, and the...Show moreCardiovascular diseases (CVD) are the leading mortality cause. Its largest underlying issue is atherosclerosis: arterial narrowing due to the buildup of cholesterol, lipids, and immune cells. High blood pressure and cholesterol levels are well-known risk factors. Despite the effectiveness of currently-available medication to improve these factors, a considerable residual risk remains, indicating the importance of other risk factors, such as age and sex. Women have a lower risk of developing CVD than men at a young age, which reverses at older age. CVD are also more common among night shift workers. The research described in this thesis used mouse models to provide new insight in the interplay between sex, age, and disturbances in day and night rhythms in atherosclerosis development, and emphasize the importance of including both men and women in scientific studies. Brown fat is one of the tissues adversely affected by disturbances in day and night rhythms and aging, and the ANGPTL4 protein was identified as an important regulator of brown fat. Inhibiting ANGPTL4 production selectively in liver cells appears a safe and promising therapeutic strategy to combat atherosclerosis. The findings also imply that time-restricted eating could be an effective tool in lowering CVD risk in shift workers.
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Atherosclerotic cardiovascular diseases
Hyperlipidemia
Sex
Age
DNA replication stress
Circadian rhythms
Circadian disturbances
Brown adipose tissue
Angiopoietin-like 4
Time-restricted eating
All authors
In het Panhuis, W.
Supervisor
Rensen, P.C.N.
Co-supervisor
Kooijman, S.; Schönke, M.
Committee
Willems van Dijk, J.A.P.; Eck, M. van; Kalsbeek, A.; Kersten, S.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2023-04-20
ISBN (print)
9789464830309

Funding

Sponsorship
The research described in this thesis was supported by the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (CVON-ENERGISE and CVON-GENIUS-II).