Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice
Silvennoinen, Reija (Wihuri Research Institute)
Quesada Vázquez, Helena (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Kareinen, Ilona (Wihuri Research Institute)
Julve i Gil, Josep (Institut d'Investigació Biomèdica Sant Pau)
Kaipiainen, Leena (Helsinki University Hospital (Finlàndia))
Gylling, Helena (Helsinki University Hospital (Finlàndia))
Blanco Vaca, Francisco (Institut d'Investigació Biomèdica Sant Pau)
Escolà-Gil, Joan Carles (Institut d'Investigació Biomèdica Sant Pau)
Kovanen, Petri T. (Wihuri Research Institute)
Lee-Rueckert, Miriam (Wihuri Research Institute)
Universitat Autònoma de Barcelona

Data:	2015
Resum:	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.
Ajuts:	Instituto de Salud Carlos III FIS 12-00291
Nota:	Altres ajuts: COST/BM0904
Drets:	Aquest 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.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Bile acids ; Physical restraint ; Psychological stress ; Reverse cholesterol transport
Publicat a:	Physiological Reports, Vol. 3 (may 2015) , ISSN 2051-817X

DOI: 10.14814/phy2.12402
PMID: 25969465

15 p, 591.7 KB

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