Variable expression of 11β Hydroxysteroid dehydrogenase (11β-HSD) isoforms in vascular endothelial cells

Vascular tissue expresses two isoforms of the enzyme 11β-Hydroxysteroid dehydrogenase, 11β-HSD1 and 11β-HSD2. These enzymes are responsible for the local metabolism of endogenous glucocorticoids (GCs). 11β-HSD1 deactivates GCs to their 11 keto metabolites or transforms inert 11 keto metabolites back to active GCs. Although, bi-directional, vascular 11β-HSD1 favors reactivation (reductase) over the deactivation (dehydrogenase) reaction, 11β-HSD2 only functions as a dehydrogenase. GC deactivation by enhanced 11β-HSD2 dehydrogenase activity or by impaired 11β-HSD1 reductase activity correlates with lower vascular resistance. These studies were designed to demonstrate the existence and regulation of these isoforms in vascular endothelial cells and to determine whether the expression varied by species and locale. Western blots were prepared from pre-confluent and confluent cultures of human umbilical vein endothelial cells (HUVEC). 11β-HSD1 was clearly expressed while 11β-HSD2 was much less prominent. Cultured rat aortic and bovine glomerular endothelial cells showed a similar pattern. Using immunohistochemistry, endothelial cells from human and mouse artery preparations clearly demonstrated 11β-HSD1. In separate experiments, pre-confluent growing HUVEC expressed more 11β-HSD1 compared to confluent cells. Serum-deprived growth-retarded HUVEC expressed significantly less 11β-HSD1. The enhanced expression of 11β-HSD1 was also observed 24 h following a scratch “injury” to the culture plates. Changes in 11β-HSD1 with growth and during repair occurred at the transcription level. Thus, 11β-HSD1 protein expression predominates in endothelial cells and varies during periods of growth.