(Hypertension. 1998;31:459.)
© 1998 American Heart Association, Inc.
Scientific Contributions |
Localization of 2 11ß-OH Steroid Dehydrogenase Isoforms in Aortic Endothelial Cells
From the Brown University School of Medicine; Rhode Island and Miriam Hospitals; Departments of Pediatrics (Nephrology) and Laboratory Medicine, Providence RI.
Correspondence to Andrew S. Brem, MD, Division of Pediatric Nephrology, Rhode Island Hospital, 593 Eddy Street, Providence RI 02903. E-mail: Andrew_Brem{at}Brown.edu
11ß-hydroxysteroid dehydrogenase (11ß-HSD) is expressed in vascular smooth muscle cells (VSMC) but has not been reported to be present in vascular endothelial cells. This enzyme assists in regulating the cellular concentration of active endogenous glucocorticoids (GCs). We have observed that endothelium intact rat aortic rings express message for both Type 1 and Type 2 11ß-HSD whereas primary cultures of VSMC express only mRNA for the Type I isoform. Since GCs diminish prostacyclin synthesis in endothelial cells, we hypothesized that 11ß-HSD is present in vascular endothelial cells. In primary cultures of rat aortic endothelial (RAE) cells, mRNA from both isoforms of 11ß-HSD could be detected by RT-PCR with higher levels of the Type 1 isoform. The oxo-reductase reaction "activating" 11-dehydro metabolites back to the parent steroid is the preferred enzyme direction (12:1 after a 120 minutes steroid incubation) in intact RAE cells. When RAE cells are grown in the presence of antisense oligonucleotides specific for Type 1 11ß-HSD, oxo-reductase activity is decreased by approximately 50% but the dehydrogenase reaction, which inactivates endogenous GCs and is characteristic of the Type 2 isoform, is unaffected. Thus endothelial cells appear to express both isoforms of 11ß-HSD; the Type 1 isoform dominates functioning in the oxo-reductase mode. Inhibition of the oxo-reductase reaction may lower the local concentrations of GC and indirectly allow for increased production of prostacyclin in endothelial cells.
Key Words: endothelial cells • glucocorticoids • 11ß-hydroxysteroid dehydrogenase • hypertension • corticosterone
Abbreviations: 11ß-HSD = 11ß-hydroxysteroid dehydrogenase • GC = glucocorticoid • VSMC = vascular smooth muscle cells • RAE = rat aortic endothelial • LDL = low density lipoprotein • VSM = vascular smooth muscle
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