Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation
Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/inhibition causes hypertension, whereas deficiency/inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2013 |
|---|---|
| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
Current atherosclerosis reports - 15(2013), 5 vom: 10. Mai, Seite 320 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hadoke, Patrick W F [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
11-beta-Hydroxysteroid Dehydrogenase Type 1 |
|---|
| Anmerkungen: |
Date Completed 09.09.2013 Date Revised 09.03.2022 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1007/s11883-013-0320-1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM225973863 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM225973863 | ||
| 003 | DE-627 | ||
| 005 | 20231224070357.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2013 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s11883-013-0320-1 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0753.xml |
| 035 | |a (DE-627)NLM225973863 | ||
| 035 | |a (NLM)23512604 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hadoke, Patrick W F |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Modulation of 11β-hydroxysteroid dehydrogenase as a strategy to reduce vascular inflammation |
| 264 | 1 | |c 2013 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 09.09.2013 | ||
| 500 | |a Date Revised 09.03.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macrophage and lymphocyte infiltration. Although acutely glucocorticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorticoid action within the lesion may reduce neointimal proliferation and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydrogenases (11β-HSDs). 11β-HSD2 converts active glucocorticoids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency/inhibition causes hypertension, whereas deficiency/inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency/inhibition is atheroprotective, whereas 11β-HSD2-deficiency accelerates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of glucocorticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Review | |
| 650 | 7 | |a Glucocorticoids |2 NLM | |
| 650 | 7 | |a 11-beta-Hydroxysteroid Dehydrogenase Type 1 |2 NLM | |
| 650 | 7 | |a EC 1.1.1.146 |2 NLM | |
| 650 | 7 | |a 11-beta-Hydroxysteroid Dehydrogenase Type 2 |2 NLM | |
| 650 | 7 | |a EC 1.1.1.146 |2 NLM | |
| 700 | 1 | |a Kipari, Tiina |e verfasserin |4 aut | |
| 700 | 1 | |a Seckl, Jonathan R |e verfasserin |4 aut | |
| 700 | 1 | |a Chapman, Karen E |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Current atherosclerosis reports |d 1999 |g 15(2013), 5 vom: 10. Mai, Seite 320 |w (DE-627)NLM110370473 |x 1534-6242 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2013 |g number:5 |g day:10 |g month:05 |g pages:320 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s11883-013-0320-1 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2013 |e 5 |b 10 |c 05 |h 320 | ||