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

doi:10.1016/j.biochi.2012.08.007

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 journal › Article › peer-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 language	English
Pages (from-to)	548-55
Number of pages	8
Journal	Biochemistry and Cell Biology
Volume	95
Issue number	3
DOIs	https://doi.org/10.1016/j.biochi.2012.08.007
Publication status	Published - 2013

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10.1016/j.biochi.2012.08.007

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
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@article{e1d6b8b46b81452c8033ec0323f35513,

title = "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",

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 ",

author = "Tijana Miti{\'c} and Ruth Andrew and Walker, {Brian R} and Hadoke, {Patrick W F}",

note = "TM received a PhD studentship from the Wellcome Trust and the work was supported by funding from the British Heart Foundation. The authors would like to acknowledge support from the BHF Centre of Research Excellence Award.",

year = "2013",

doi = "10.1016/j.biochi.2012.08.007",

language = "English",

volume = "95",

pages = "548--55",

journal = "Biochemistry and Cell Biology",

issn = "1208-6002",

publisher = "National Research Council of Canada",

number = "3",

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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. / Mitić, Tijana; Andrew, Ruth; Walker, Brian R et al.
In: Biochemistry and Cell Biology, Vol. 95, No. 3, 2013, p. 548-55.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Mitić, Tijana

AU - Andrew, Ruth

AU - Walker, Brian R

AU - Hadoke, Patrick W F

N1 - TM received a PhD studentship from the Wellcome Trust and the work was supported by funding from the British Heart Foundation. The authors would like to acknowledge support from the BHF Centre of Research Excellence Award.

PY - 2013

Y1 - 2013

N2 - 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

AB - 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

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DO - 10.1016/j.biochi.2012.08.007

M3 - Article

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SN - 1208-6002

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JO - Biochemistry and Cell Biology

JF - Biochemistry and Cell Biology

IS - 3

ER -

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

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