11β-Hydroxysteroid dehydrogenase type 1 contributes to the regulation of 7-oxysterol levels in the arterial wall through the inter-conversion of 7-ketocholesterol and 7β-hydroxycholesterol

Tijana Mitić, Ruth Andrew, Brian R Walker, Patrick W F Hadoke

Research output: Contribution to journalArticlepeer-review

Abstract

The atherogenic 7-oxysterols, 7-ketocholesterol (7-KC) and 7β-hydroxycholesterol (7βOHC), can directly impair arterial function. Inter-conversion of 7-KC and 7βOHC has recently been shown as a novel role for the glucocorticoid-metabolizing enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). Since this enzyme is expressed in vascular smooth muscle cells, we addressed the hypothesis that inter-conversion of 7-KC and 7βOHC by 11β-HSD1 may contribute to regulation of arterial function. Incubation (4-24 h) of aortic rings with either 7-KC (25 μM) or 7βOHC (20 μM) had no effect on endothelium-dependent (acetylcholine) or -independent (sodium nitroprusside) relaxation. In contrast, exposure to 7-KC (but not to 7βOHC) attenuated noradrenaline-induced contraction (E(max)) after 4 h (0.78 ± 0.28 vs 0.40 ± 0.08 mN/mm; p 
Original languageEnglish
Pages (from-to)548-55
Number of pages8
JournalBiochemistry and Cell Biology
Volume95
Issue number3
DOIs
Publication statusPublished - 2013

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