Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice
Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway....
| Autores: | , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2015 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:185330 |
| Acceso en línea: | https://ddd.uab.cat/record/185330 https://dx.doi.org/urn:doi:10.14814/phy2.12402 |
| Access Level: | acceso abierto |
| Palabra clave: | Bile acids Physical restraint Psychological stress Reverse cholesterol transport |
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Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in miceSilvennoinen, ReijaQuesada Vázquez, Helena|||0000-0001-6854-6569Kareinen, IlonaJulve i Gil, Josep|||0000-0002-6531-2246Kaipiainen, LeenaGylling, HelenaBlanco Vaca, Francisco|||0000-0001-7380-5385Escolà-Gil, Joan Carles|||0000-0001-9021-2485Kovanen, Petri T.Lee-Rueckert, MiriamBile acidsPhysical restraintPsychological stressReverse cholesterol transportPsychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7 α -hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress.Universitat Autònoma de Barcelona 22015-01-0120152015-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/185330https://dx.doi.org/urn:doi:10.14814/phy2.12402reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengInstituto de Salud Carlos III https://doi.org/10.13039/501100004587 FIS12-00291open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1853302026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice |
| title |
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice |
| spellingShingle |
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice Silvennoinen, Reija Bile acids Physical restraint Psychological stress Reverse cholesterol transport |
| title_short |
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice |
| title_full |
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice |
| title_fullStr |
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice |
| title_full_unstemmed |
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice |
| title_sort |
Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice |
| dc.creator.none.fl_str_mv |
Silvennoinen, Reija Quesada Vázquez, Helena|||0000-0001-6854-6569 Kareinen, Ilona Julve i Gil, Josep|||0000-0002-6531-2246 Kaipiainen, Leena Gylling, Helena Blanco Vaca, Francisco|||0000-0001-7380-5385 Escolà-Gil, Joan Carles|||0000-0001-9021-2485 Kovanen, Petri T. Lee-Rueckert, Miriam |
| author |
Silvennoinen, Reija |
| author_facet |
Silvennoinen, Reija Quesada Vázquez, Helena|||0000-0001-6854-6569 Kareinen, Ilona Julve i Gil, Josep|||0000-0002-6531-2246 Kaipiainen, Leena Gylling, Helena Blanco Vaca, Francisco|||0000-0001-7380-5385 Escolà-Gil, Joan Carles|||0000-0001-9021-2485 Kovanen, Petri T. Lee-Rueckert, Miriam |
| author_role |
author |
| author2 |
Quesada Vázquez, Helena|||0000-0001-6854-6569 Kareinen, Ilona Julve i Gil, Josep|||0000-0002-6531-2246 Kaipiainen, Leena Gylling, Helena Blanco Vaca, Francisco|||0000-0001-7380-5385 Escolà-Gil, Joan Carles|||0000-0001-9021-2485 Kovanen, Petri T. Lee-Rueckert, Miriam |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona |
| dc.subject.none.fl_str_mv |
Bile acids Physical restraint Psychological stress Reverse cholesterol transport |
| topic |
Bile acids Physical restraint Psychological stress Reverse cholesterol transport |
| description |
Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7 α -hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. |
| publishDate |
2015 |
| dc.date.none.fl_str_mv |
2 2015-01-01 2015 2015-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/185330 https://dx.doi.org/urn:doi:10.14814/phy2.12402 |
| url |
https://ddd.uab.cat/record/185330 https://dx.doi.org/urn:doi:10.14814/phy2.12402 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 FIS12-00291 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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