Glucocorticoid response elements and 11β-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression

Liu, Yong; Mladinov, Domagoj; Pietrusz, Jennifer L.; Usa, Kristie; Liang, Mingyu

doi:10.1093/cvr/cvn231

Cited by 80 publications

(82 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another possibility is that excess glucocorticoids may suppress endothelial nitric oxide synthase as we recently demonstrated (26). It is also possible that excess glucocorticoids may exacerbate oxidative stress (20).…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

Liu

Singh

Usa

et al. 2008

Physiological Genomics

Self Cite

View full text Add to dashboard Cite

Liu Y, Singh RJ, Usa K, Netzel BC, Liang M. Renal medullary 11␤-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension. Physiol Genomics 36: 52-58, 2008. First published September 30, 2008 doi:10.1152/physiolgenomics.90283.2008.-The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11␤-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11␤-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13 BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11␤-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocorticosterone to active corticosterone. The urinary corticosterone/11-dehydrocorticosterone ratio as well as urinary excretion of corticosterone was higher in Dahl salt-sensitive rats than in SS-13 BN rats. Knockdown of renal medullary 11␤-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinary excretion of corticosterone. Knockdown of 11␤-hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13 BN rats. Long-term attenuation of salt-induced hypertension was achieved with small hairpin RNA targeting renal medullary 11␤-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11␤-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.

show abstract

Section: Discussionmentioning

confidence: 95%

“…Small interfering RNA (siRNA) was designed and synthesized similar to that described previously (23,26,27). The rat 11␤-HSD1 target sequence was 5Ј-aagcaaucagagguugggucauu-3Ј.…”

Section: Methodsmentioning

confidence: 99%

Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

Liu

Singh

Usa

et al. 2008

Physiological Genomics

Self Cite

View full text Add to dashboard Cite

show abstract

“…[17][18][19] IVD delivers sustained release of corticosteroid and has proven to be an effective treatment modality for DMO. [9][10][11][12] Corticosteroids block production of inflammatory cytokines and VEGF, 27 inhibit leukostasis, 28 improve the barrier function of vascular endothelial cell tight junctions, 29 inhibit endothelial nitric oxide synthase, 30 reduce tissue oedema, and decrease the release of prostaglandins and histamines, 31 all of which could cause vasodilation and choroidal thickening, potentially affecting ocular perfusion pressure. 32 IVD, therefore, could exert its therapeutic effect not only on the retina, but also on the choroid, by decreasing the production of inflammatory cytokines and factors that could increase CT.…”

Section: Discussionmentioning

confidence: 99%

Effect of intravitreal dexamethasone implant on retinal and choroidal thickness in refractory diabetic macular oedema after multiple anti-VEGF injections

Kim

Cho

Lee

et al. 2016

Eye

View full text Add to dashboard Cite

Aims To investigate the effect of intravitreal dexamethasone implant (IVD) on central foveal thickness (CFT), choroidal thickness (CT) and its correlation with visual acuity in eyes with refractory diabetic macular oedema (DMO). Methods This was a retrospective interventional case-series. Thirty-five eyes of 35 patients were treated with a single injection of IVD because of refractory DMO with CFT over 300 μm, and persistent intraretinal and subretinal fluid despite of multiple intravitreal bevacizumab injections. Patients were followed-up for 6 months for the evaluation of CFT and subfoveal CT by spectral-domain optical coherence tomography. Results All eyes (mean age: 59.4 ± 12.35 years; 18 males, 17 females) had been previously treated with multiple bevacizumab injections and showed persistent DMO (mean number of injections 4.08 ± 2.98) The preoperative logMAR BCVA was 0.49 ± 0.24, which gradually improved to 0.46 ± 0.32 at 6 months (P = 0.652) and 26% gained two or more lines of Snellen visual acuity. At baseline, the mean CFT was 526.29 ± 123.48 μm, which significantly improved to 316.15 ± 100.09 μm at 3 months (Po0.001). However, CFT deteriorated to 457.07 ± 136.53 μm at 6 months (P = 0.051). Similarly, the mean preoperative subfoveal CT was 288.91 ± 36.47 μm and it decreased to 266.85 ± 30.93 μm at 3 months (Po0.01), but increased to 278.63 ± 32.55 μm at 6 months (P = 0.137). The reduction of CFT from baseline showed significant correlation with that of subfoveal CT at 3 months (P = 0.041) and at 6 months (P = 0.008). Conclusions In DMO refractory to multiple bevacizumab injections, IVD significantly reduced CFT and subfoveal CT, with BCVA improvement in one-fourth of the patients. The reduction of CFT showed significant correlation with reduction of subfoveal CT.

show abstract

“…A caveat to these salutary effects, however, would be a potential for an undesirable increase in angiogenesis in disease states such as cancer and diabetic retinopathy of which there is increased risk with obesity and metabolic syndrome. Both 11 -HSD1 and 11 -HSD2 appear to be expressed in human endothelial cells, and modulate inducible nitric oxide synthase (iNOS) activity (Liu et al, 2008). The story in rodents is less clear, but suggests that expression of 11 -HSD isoforms may be both species and anatomical (perhaps fat depot) site-specific (Hadoke et al, 2006).…”

Section: Blood Vessels and The Vascular Wall -Glucocorticoids Are Angmentioning

confidence: 99%

Obesity and corticosteroids: 11β-Hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

Morton

2010

Molecular and Cellular Endocrinology

149

159

View full text Add to dashboard Cite

Glucocorticoid response elements and 11β-hydroxysteroid dehydrogenases in the regulation of endothelial nitric oxide synthase expression

Abstract: We identified the first GRE in the eNOS promoter region and demonstrated that endogenous 11 beta-HSD1 and 11 beta-HSD2 play significant and distinct roles in modulating the effect of glucocorticoids on eNOS expression.

Cited by 80 publications

References 41 publications

Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension

Effect of intravitreal dexamethasone implant on retinal and choroidal thickness in refractory diabetic macular oedema after multiple anti-VEGF injections

Obesity and corticosteroids: 11β-Hydroxysteroid type 1 as a cause and therapeutic target in metabolic disease

Contact Info

Product

Resources

About