PMID- 23303209
OWN - NLM
STAT- MEDLINE
DCOM- 20130617
LR  - 20230614
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Print)
IS  - 0892-6638 (Linking)
VI  - 27
IP  - 4
DP  - 2013 Apr
TI  - 11beta-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells 
      reduces atherosclerosis.
PG  - 1519-31
LID - 10.1096/fj.12-219105 [doi]
AB  - 11beta-Hydroxysteroid dehydrogenase type-1 (11beta-HSD1) converts inert cortisone into 
      active cortisol, amplifying intracellular glucocorticoid action. 11beta-HSD1 
      deficiency improves cardiovascular risk factors in obesity but exacerbates acute 
      inflammation. To determine the effects of 11beta-HSD1 deficiency on atherosclerosis 
      and its inflammation, atherosclerosis-prone apolipoprotein E-knockout (ApoE-KO) 
      mice were treated with a selective 11beta-HSD1 inhibitor or crossed with 11beta-HSD1-KO 
      mice to generate double knockouts (DKOs) and challenged with an atherogenic 
      Western diet. 11beta-HSD1 inhibition or deficiency attenuated atherosclerosis 
      (74-76%) without deleterious effects on plaque structure. This occurred without 
      affecting plasma lipids or glucose, suggesting independence from classical 
      metabolic risk factors. KO plaques were not more inflamed and indeed had 36% less 
      T-cell infiltration, associated with 38% reduced circulating monocyte 
      chemoattractant protein-1 (MCP-1) and 36% lower lesional vascular cell adhesion 
      molecule-1 (VCAM-1). Bone marrow (BM) cells are key to the atheroprotection, 
      since transplantation of DKO BM to irradiated ApoE-KO mice reduced 
      atherosclerosis by 51%. 11beta-HSD1-null macrophages show 76% enhanced cholesterol 
      ester export. Thus, 11beta-HSD1 deficiency reduces atherosclerosis without 
      exaggerated lesional inflammation independent of metabolic risk factors. 
      Selective 11beta-HSD1 inhibitors promise novel antiatherosclerosis effects over and 
      above their benefits for metabolic risk factors via effects on BM cells, 
      plausibly macrophages.
FAU - Kipari, Tiina
AU  - Kipari T
AD  - British Heart Foundation Centre for Cardiovascular Science, The Queen's Medical 
      Research Institute, University of Edinburgh, Edinburgh, UK. tkipari@ed.ac.uk
FAU - Hadoke, Patrick W F
AU  - Hadoke PW
FAU - Iqbal, Javaid
AU  - Iqbal J
FAU - Man, Tak-Yung
AU  - Man TY
FAU - Miller, Eileen
AU  - Miller E
FAU - Coutinho, Agnes E
AU  - Coutinho AE
FAU - Zhang, Zhenguang
AU  - Zhang Z
FAU - Sullivan, Katie M
AU  - Sullivan KM
FAU - Mitic, Tijana
AU  - Mitic T
FAU - Livingstone, Dawn E W
AU  - Livingstone DE
FAU - Schrecker, Christopher
AU  - Schrecker C
FAU - Samuel, Kay
AU  - Samuel K
FAU - White, Christopher I
AU  - White CI
FAU - Bouhlel, M Amine
AU  - Bouhlel MA
FAU - Chinetti-Gbaguidi, Giulia
AU  - Chinetti-Gbaguidi G
FAU - Staels, Bart
AU  - Staels B
FAU - Andrew, Ruth
AU  - Andrew R
FAU - Walker, Brian R
AU  - Walker BR
FAU - Savill, John S
AU  - Savill JS
FAU - Chapman, Karen E
AU  - Chapman KE
FAU - Seckl, Jonathan R
AU  - Seckl JR
LA  - eng
GR  - G0802069/MRC_/Medical Research Council/United Kingdom
GR  - 083184/Z/07/Z/WT_/Wellcome Trust/United Kingdom
GR  - 86642/MRC_/Medical Research Council/United Kingdom
GR  - MR/K026992/1/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - G0800235/MRC_/Medical Research Council/United Kingdom
GR  - G9900991/MRC_/Medical Research Council/United Kingdom
GR  - RG/11/4/28734/BHF_/British Heart Foundation/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130109
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Glucocorticoids)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenase Type 1)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenase Type 1/antagonists & 
      inhibitors/*deficiency/metabolism
MH  - Adipose Tissue/drug effects/metabolism
MH  - Animals
MH  - Atherosclerosis/genetics/*metabolism
MH  - Bone Marrow/drug effects/*metabolism
MH  - Glucocorticoids/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Risk Factors
MH  - Vascular Cell Adhesion Molecule-1/metabolism
PMC - PMC3606528
EDAT- 2013/01/11 06:00
MHDA- 2013/06/19 06:00
PMCR- 2013/04/01
CRDT- 2013/01/11 06:00
PHST- 2013/01/11 06:00 [entrez]
PHST- 2013/01/11 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - fj.12-219105 [pii]
AID - 12-219105 [pii]
AID - 10.1096/fj.12-219105 [doi]
PST - ppublish
SO  - FASEB J. 2013 Apr;27(4):1519-31. doi: 10.1096/fj.12-219105. Epub 2013 Jan 9.