11β-Hydroxysteroid dehydrogenase activity in human aortic smooth muscle cells

Abstract

11β-Hydroxysteroid dehydrogenases (11β-HSD) interconvert cortisol, the physiological glucocorticoid, and its inactive metabolite cortisone in humans. There are two isoforms. The type 1 isoform (11β-HSD1) catalyzes both 11β-dehydrogenation (cortisol to cortisone) and the reverse oxoreduction (cortisone to cortisol), but the type 2 isoform (11β-HSD2) catalyzes only 11β-dehydrogenation. The diminished dehydrogenase activity has been demonstrated in resistance vessels of genetically hypertensive rats. However, the isoform(s) that plays a significant role in conferring the dehydrogenase activity on vasculature has not been determined. We investigated 11β-HSD activities in human vascular smooth muscle cells by manipulating 11β-HSD expressions with antisense oligonucleotides. The results showed that 11β-HSD2 dominates functioning in the dehydrogenase mode in these cells. This indicates that impairment of 11β-HSD2 activity in vascular wall may be related to the pathogenesis of hypertension.