title: Both transient and continuous corticosterone excess inhibit atherosclerotic plaque formation in APOE*3-leiden.CETP mice.
abstract: BACKGROUND
  The role of glucocorticoids in atherosclerosis development is not clearly established. Human studies show a clear association between glucocorticoid excess and cardiovascular disease, whereas most animal models indicate an inhibitory effect of glucocorticoids on atherosclerosis development. These animal models, however, neither reflect long-term glucocorticoid overexposure nor display human-like lipoprotein metabolism.
  
  
  OBJECTIVE
  To investigate the effects of transient and continuous glucocorticoid excess on atherosclerosis development in a mouse model with human-like lipoprotein metabolism upon feeding a Western-type diet.
  
  
  METHODS
  Pair-housed female APOE*3-Leiden.CETP (E3L.CETP) mice fed a Western-type containing 0.1% cholesterol for 20 weeks were given corticosterone (50 µg/ml) for either 5 (transient group) or 17 weeks (continuous group), or vehicle (control group) in the drinking water. At the end of the study, atherosclerosis severity, lesion area in the aortic root, the number of monocytes adhering to the endothelial wall and macrophage content of the plaque were measured.
  
  
  RESULTS
  Corticosterone treatment increased body weight and food intake for the duration of the treatment and increased gonadal and subcutaneous white adipose tissue weight in transient group by +35% and +31%, and in the continuous group by +140% and 110%. Strikingly, both transient and continuous corticosterone treatment decreased total atherosclerotic lesion area by -39% without lowering plasma cholesterol levels. In addition, there was a decrease of -56% in macrophage content of the plaque with continuous corticosterone treatment, and a similar trend was present with the transient treatment.
  
  
  CONCLUSIONS
  Increased corticosterone exposure in mice with human-like lipoprotein metabolism has beneficial, long-lasting effects on atherosclerosis, but negatively affects body fat distribution by promoting fat accumulation in the long-term. This indicates that the increased atherosclerosis observed in humans in states of glucocorticoid excess may not be related to cortisol per se, but might be the result of complex indirect effects of cortisol.
authors.affiliation: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands. h.e.auvinen@lumc.nl
authors.forename: Hanna E
authors.initials: HE
authors.lastname: Auvinen
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.forename: Hans
authors.initials: H
authors.lastname: Princen
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Romijn
authors.forename: Louis M
authors.initials: LM
authors.lastname: Havekes
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Onno C
authors.initials: OC
authors.lastname: Meijer
authors.forename: Nienke R
authors.initials: NR
authors.lastname: Biermasz
authors.forename: Patrick C N
authors.initials: PC
authors.lastname: Rensen
authors.forename: Alberto M
authors.initials: AM
authors.lastname: Pereira
mesh_terms: D000273:Adipose Tissue; D000821:Animal Feed; D000818:Animals; D053318:Apolipoprotein E3 / Q000378:metabolism*; D050197:Atherosclerosis / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D001823:Body Composition; D001835:Body Weight / Q000502:physiology; D002784:Cholesterol / Q000097:blood; D002940:Circadian Rhythm / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism*; D004032:Diet; D004435:Eating / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*
chemical_list: D053318:Apolipoprotein E3; D005938:Glucocorticoids; D007328:Insulin; D008055:Lipids; D008074:Lipoproteins; D002784:Cholesterol; D003345:Corticosterone