11β-hydroxysteroid dehydrogenase type 1 deficiency in bone marrow-derived cells reduces atherosclerosis.
Tiina Kipari, Patrick WF Hadoke, Javaid Iqbal, Tak-Yung Man, Eileen Miller, Agnes E Coutinho, Zhenguang Zhang, Katie M Sullivan, Tijana Mitic, Dawn EW Livingstone, Christopher Schrecker, Kay Samuel, Christopher I White, M Amine Bouhlel, Giulia Chinetti-Gbaguidi, Bart Staels, Ruth Andrew, Brian R Walker, John S Savill, Karen E Chapman Show all
FASEB J | Published : 2013
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, atherosclerosis-prone 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..View full abstract
Awarded by Medical Research Council
Awarded by British Heart Foundation
Awarded by Wellcome Trust