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11beta-Hydroxysteroid dehydrogenase type 1-driven cortisone reactivation regulates plasminogen activator inhibitor type 1 in adipose tissue of obese women.
J Thromb Haemost 2006; 4(3):621-7JT

Abstract

BACKGROUND

Plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of the fibrinolytic system and contributes to an increased risk of atherothrombosis in insulin-resistant obese patients. In adipose tissue, we have shown that PAI-1 is synthesized mainly in the visceral stromal compartment and is positively regulated by glucocorticoids. We have demonstrated that adipose tissue expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), an enzyme that catalyzes the conversion of inactive cortisone to active cortisol, is exaggerated in obese patients.

OBJECTIVES

We hypothesized that increased action of 11beta-HSD-1 in adipose tissue of obese subjects may contribute to PAI-1 overproduction.

PATIENTS AND METHODS

Using in situ hybridization, we studied the expression of the mRNAs coding for PAI-1 and 11beta-HSD-1 in the stromal compartment of visceral adipose tissue obtained from obese women. The regulation of PAI-1 secretion from in vitro incubated tissue explants was also investigated.

RESULTS

Regression analysis showed a significant positive linear relationship between PAI-1 and 11beta-HSD-1 mRNAs expression. In vitro incubation of adipose tissue explants demonstrated that cortisone stimulated PAI-1 gene expression and secretion, and that these effects were inhibited by co-incubation with the 11beta-HSD inhibitor, glycyrrhetinic acid.

CONCLUSIONS

Our data demonstrate that 11beta-HSD-1-driven cortisone reactivation regulates adipose PAI-1 synthesis and secretion. They suggest that the increased PAI-1 synthesis and secretion observed in obese patients can be also related, at least in part, to an increased local conversion of cortisone to cortisol. Therefore, local cortisol metabolism in adipose tissue may be involved in increasing the risk of cardiovascular disease in obese subjects.

Authors+Show Affiliations

INSERM U626, Université de la Méditerranée, Marseilles and Faculté de Médecine, Université de la Méditerranée, Marseilles, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16460444

Citation

Ayachi, S Ei, et al. "11beta-Hydroxysteroid Dehydrogenase Type 1-driven Cortisone Reactivation Regulates Plasminogen Activator Inhibitor Type 1 in Adipose Tissue of Obese Women." Journal of Thrombosis and Haemostasis : JTH, vol. 4, no. 3, 2006, pp. 621-7.
Ayachi SE, Paulmyer-Lacroix O, Verdier M, et al. 11beta-Hydroxysteroid dehydrogenase type 1-driven cortisone reactivation regulates plasminogen activator inhibitor type 1 in adipose tissue of obese women. J Thromb Haemost. 2006;4(3):621-7.
Ayachi, S. E., Paulmyer-Lacroix, O., Verdier, M., Alessi, M. C., Dutour, A., & Grino, M. (2006). 11beta-Hydroxysteroid dehydrogenase type 1-driven cortisone reactivation regulates plasminogen activator inhibitor type 1 in adipose tissue of obese women. Journal of Thrombosis and Haemostasis : JTH, 4(3), pp. 621-7.
Ayachi SE, et al. 11beta-Hydroxysteroid Dehydrogenase Type 1-driven Cortisone Reactivation Regulates Plasminogen Activator Inhibitor Type 1 in Adipose Tissue of Obese Women. J Thromb Haemost. 2006;4(3):621-7. PubMed PMID: 16460444.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 11beta-Hydroxysteroid dehydrogenase type 1-driven cortisone reactivation regulates plasminogen activator inhibitor type 1 in adipose tissue of obese women. AU - Ayachi,S Ei, AU - Paulmyer-Lacroix,O, AU - Verdier,M, AU - Alessi,M-C, AU - Dutour,A, AU - Grino,M, PY - 2006/2/8/pubmed PY - 2006/5/25/medline PY - 2006/2/8/entrez SP - 621 EP - 7 JF - Journal of thrombosis and haemostasis : JTH JO - J. Thromb. Haemost. VL - 4 IS - 3 N2 - BACKGROUND: Plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of the fibrinolytic system and contributes to an increased risk of atherothrombosis in insulin-resistant obese patients. In adipose tissue, we have shown that PAI-1 is synthesized mainly in the visceral stromal compartment and is positively regulated by glucocorticoids. We have demonstrated that adipose tissue expression of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD-1), an enzyme that catalyzes the conversion of inactive cortisone to active cortisol, is exaggerated in obese patients. OBJECTIVES: We hypothesized that increased action of 11beta-HSD-1 in adipose tissue of obese subjects may contribute to PAI-1 overproduction. PATIENTS AND METHODS: Using in situ hybridization, we studied the expression of the mRNAs coding for PAI-1 and 11beta-HSD-1 in the stromal compartment of visceral adipose tissue obtained from obese women. The regulation of PAI-1 secretion from in vitro incubated tissue explants was also investigated. RESULTS: Regression analysis showed a significant positive linear relationship between PAI-1 and 11beta-HSD-1 mRNAs expression. In vitro incubation of adipose tissue explants demonstrated that cortisone stimulated PAI-1 gene expression and secretion, and that these effects were inhibited by co-incubation with the 11beta-HSD inhibitor, glycyrrhetinic acid. CONCLUSIONS: Our data demonstrate that 11beta-HSD-1-driven cortisone reactivation regulates adipose PAI-1 synthesis and secretion. They suggest that the increased PAI-1 synthesis and secretion observed in obese patients can be also related, at least in part, to an increased local conversion of cortisone to cortisol. Therefore, local cortisol metabolism in adipose tissue may be involved in increasing the risk of cardiovascular disease in obese subjects. SN - 1538-7933 UR - https://www.unboundmedicine.com/medline/citation/16460444/11beta_Hydroxysteroid_dehydrogenase_type_1_driven_cortisone_reactivation_regulates_plasminogen_activator_inhibitor_type_1_in_adipose_tissue_of_obese_women_ L2 - https://doi.org/10.1111/j.1538-7836.2006.01811.x DB - PRIME DP - Unbound Medicine ER -