Light‐Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes
Background Despite compelling epidemiological evidence that circadian disruption inherent to long‐term shift work enhances atherosclerosis progression and vascular events, the underlying mechanisms remain poorly understood. A challenge to the use of mouse models for mechanistic and interventional st...
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| Format: | Article |
| Language: | English |
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Wiley
2021-01-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.120.018151 |
| _version_ | 1827746709766144000 |
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| author | Mariana G. Figueiro Young‐Hwa Goo Ryan Hogan Barbara Plitnick Jeong‐Kyung Lee Kiran Jahangir Mousumi Moulik Vijay K. Yechoor Antoni Paul |
| author_facet | Mariana G. Figueiro Young‐Hwa Goo Ryan Hogan Barbara Plitnick Jeong‐Kyung Lee Kiran Jahangir Mousumi Moulik Vijay K. Yechoor Antoni Paul |
| author_sort | Mariana G. Figueiro |
| collection | DOAJ |
| description | Background Despite compelling epidemiological evidence that circadian disruption inherent to long‐term shift work enhances atherosclerosis progression and vascular events, the underlying mechanisms remain poorly understood. A challenge to the use of mouse models for mechanistic and interventional studies involving light‐dark patterns is that the spectral and absolute sensitivities of the murine and human circadian systems are very different, and light stimuli in nocturnal mice should be scaled to represent the sensitivities of the human circadian system. Methods and Results We used calibrated devices to deliver to low‐density lipoprotein receptor knockout mice light‐dark patterns representative of that experienced by humans working day shifts or rotating shift schedules. Mice under day shifts were maintained under regular 12 hours of light and 12 hours of dark cycles. Mice under rotating shift schedules were subjected for 11 weeks to reversed light‐dark patterns 4 days in a row per week, followed by 3 days of regular light‐dark patterns. In both protocols the light phases consisted of monochromatic green light at an irradiance of 4 µW/cm2. We found that the shift work paradigm disrupts the foam cell's molecular clock and increases endoplasmic reticulum stress and apoptosis. Lesions of mice under rotating shift schedules were larger and contained less prostabilizing fibrillar collagen and significantly increased areas of necrosis. Conclusions Low‐density lipoprotein receptor knockout mice under light‐dark patterns analogous to that experienced by rotating shift workers develop larger and more vulnerable plaques and may represent a valuable model for further mechanistic and/or interventional studies against the deleterious vascular effects of rotating shift work. |
| first_indexed | 2024-03-11T05:30:08Z |
| format | Article |
| id | doaj.art-d0a4ad155eb8425c8c276b0c296eb5d0 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-03-11T05:30:08Z |
| publishDate | 2021-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-d0a4ad155eb8425c8c276b0c296eb5d02023-11-17T17:13:23ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802021-01-0110210.1161/JAHA.120.018151Light‐Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion PhenotypesMariana G. Figueiro0Young‐Hwa Goo1Ryan Hogan2Barbara Plitnick3Jeong‐Kyung Lee4Kiran Jahangir5Mousumi Moulik6Vijay K. Yechoor7Antoni Paul8Lighting Research Center Rensselaer Polytechnic Institute Troy NYDepartment of Molecular and Cellular Physiology Albany Medical College Albany NYDepartment of Molecular and Cellular Physiology Albany Medical College Albany NYLighting Research Center Rensselaer Polytechnic Institute Troy NYDivision of Endocrinology Department of Medicine Diabetes and Beta Cell Biology Center University of Pittsburgh School of Medicine Pittsburgh PADepartment of Molecular and Cellular Physiology Albany Medical College Albany NYDivision of Cardiology Department of Pediatrics UPMC Children's Hospital of PittsburghUniversity of Pittsburgh School of Medicine Pittsburgh PADivision of Endocrinology Department of Medicine Diabetes and Beta Cell Biology Center University of Pittsburgh School of Medicine Pittsburgh PADepartment of Molecular and Cellular Physiology Albany Medical College Albany NYBackground Despite compelling epidemiological evidence that circadian disruption inherent to long‐term shift work enhances atherosclerosis progression and vascular events, the underlying mechanisms remain poorly understood. A challenge to the use of mouse models for mechanistic and interventional studies involving light‐dark patterns is that the spectral and absolute sensitivities of the murine and human circadian systems are very different, and light stimuli in nocturnal mice should be scaled to represent the sensitivities of the human circadian system. Methods and Results We used calibrated devices to deliver to low‐density lipoprotein receptor knockout mice light‐dark patterns representative of that experienced by humans working day shifts or rotating shift schedules. Mice under day shifts were maintained under regular 12 hours of light and 12 hours of dark cycles. Mice under rotating shift schedules were subjected for 11 weeks to reversed light‐dark patterns 4 days in a row per week, followed by 3 days of regular light‐dark patterns. In both protocols the light phases consisted of monochromatic green light at an irradiance of 4 µW/cm2. We found that the shift work paradigm disrupts the foam cell's molecular clock and increases endoplasmic reticulum stress and apoptosis. Lesions of mice under rotating shift schedules were larger and contained less prostabilizing fibrillar collagen and significantly increased areas of necrosis. Conclusions Low‐density lipoprotein receptor knockout mice under light‐dark patterns analogous to that experienced by rotating shift workers develop larger and more vulnerable plaques and may represent a valuable model for further mechanistic and/or interventional studies against the deleterious vascular effects of rotating shift work.https://www.ahajournals.org/doi/10.1161/JAHA.120.018151atherosclerosiscircadian disruptionmiceshift work |
| spellingShingle | Mariana G. Figueiro Young‐Hwa Goo Ryan Hogan Barbara Plitnick Jeong‐Kyung Lee Kiran Jahangir Mousumi Moulik Vijay K. Yechoor Antoni Paul Light‐Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease atherosclerosis circadian disruption mice shift work |
| title | Light‐Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes |
| title_full | Light‐Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes |
| title_fullStr | Light‐Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes |
| title_full_unstemmed | Light‐Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes |
| title_short | Light‐Dark Patterns Mirroring Shift Work Accelerate Atherosclerosis and Promote Vulnerable Lesion Phenotypes |
| title_sort | light dark patterns mirroring shift work accelerate atherosclerosis and promote vulnerable lesion phenotypes |
| topic | atherosclerosis circadian disruption mice shift work |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.120.018151 |
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