Journal article
11β hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis
T Kipari, PWF Hadoke, J Iqbal, TY Man, E Miller, AE Coutinho, Z Zhang, KM Sullivan, T Mitic, DEW Livingstone, C Schrecker, K Samuel, CI White, MA Bouhlel, G Chinetti-Gbaguidi, B Staels, R Andrew, BR Walker, JS Savill, KE Chapman Show all
FASEB Journal | FEDERATION AMER SOC EXP BIOL | Published : 2013
DOI: 10.1096/fj.12-219105
Open access
Abstract
11β-Hydroxysteroid dehydrogenase type-1 (11β-HSD1) converts inert cortisone into active cortisol, amplifying intracellular glucocorticoid action. 11β- HSD1 deficiency improves cardiovascular risk factors in obesity but exacerbates acute inflammation. To determine the effects of 11β-HSD1 deficiency on atherosclerosis and its inflammation, atherosclerosisprone apolipoprotein E-knockout (ApoE-KO) mice were treated with a selective 11β-HSD1 inhibitor or crossed with 11β-HSD1-KO mice to generate double knockouts (DKOs) and challenged with an atherogenic Western diet. 11β-HSD1 inhibition or deficiency attenuated atherosclerosis (74-76%) without deleterious effects on plaque structure. This occurre..
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Awarded by Medical Research Council
Funding Acknowledgements
The authors thank Dr. Valerie S. Densmore for generating the original 11 beta-HSD1, ApoE double-knockout line, and Dr. Nicholas Kirkby for help with optical projection tomography. This work was supported by grants from the Wellcome Trust (program grant 083184/Z/07/Z), the Medical Research Council (project grant 86642), the Society for Endocrinology, the British Heart Foundation (BHF), Agence Nationale de la Recherche (AlMHA project), and the Carnegie Trust. The authors acknowledge the support of the BHF Centre of Excellence. Conflict of interest: B. R. W. and J.R.S. hold intellectual property on the concept of 11 beta-HSD1 inhibitors in metabolic and cardiovascular disease.