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11β‐Hydroxysteroid dehydrogenase type 1‐driven cortisone reactivation regulates plasminogen activator inhibitor type 1 in adipose tissue of obese women
Author(s) -
AYACHI S. EI,
PAULMYERLACROIX O.,
VERDIER M.,
ALESSI M.C.,
DUTOUR A.,
GRINO M.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2006.01811.x
Subject(s) - adipose tissue , 11β hydroxysteroid dehydrogenase type 1 , cortisone , medicine , endocrinology , adipose tissue macrophages , plasminogen activator inhibitor 1 , white adipose tissue , plasminogen activator , stromal cell , secretion , biology , chemistry , dehydrogenase , enzyme , biochemistry
Summary. 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 11β‐hydroxysteroid dehydrogenase type 1 (11β‐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 11β‐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 11β‐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 11β‐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 11β‐HSD inhibitor, glycyrrhetinic acid. Conclusions: Our data demonstrate that 11β‐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.