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; Jonathan R Seckl

Journal article

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

DOI: 10.1096/fj.12-219105

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, 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..

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