Variable expression of 11beta Hydroxysteroid dehydrogenase (11beta-HSD) isoforms in vascular endothelial cells.
Vascular tissue expresses two isoforms of the enzyme 11beta-Hydroxysteroid dehydrogenase, 11beta-HSD1 and 11beta-HSD2. These enzymes are responsible for the local metabolism of endogenous glucocorticoids (GCs). 11beta-HSD1 deactivates GCs to their 11keto metabolites or transforms inert 11keto metabolites back to active GCs. Although, bi-directional, vascular 11beta-HSD1 favors reactivation (reductase) over the deactivation (dehydrogenase) reaction, 11beta-HSD2 only functions as a dehydrogenase. GC deactivation by enhanced 11beta-HSD2 dehydrogenase activity or by impaired 11beta-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). 11beta-HSD1 was clearly expressed while 11beta-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 11beta-HSD1. In separate experiments, pre-confluent growing HUVEC expressed more 11beta-HSD1 compared to confluent cells. Serum-deprived growth-retarded HUVEC expressed significantly less 11beta-HSD1. The enhanced expression of 11beta-HSD1 was also observed 24h following a scratch "injury" to the culture plates. Changes in 11beta-HSD1 with growth and during repair occurred at the transcription level. Thus, 11beta-HSD1 protein expression predominates in endothelial cells and varies during periods of growth.
Rhode Island Hospital, Division of Kidney Diseases and Hypertension, Brown Medical School, Providence, RI 02903, United States.
Rujun
R
Gong
David J
DJ
Morris
Andrew S
AS
Brem
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000201:enzymology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D042783:Endothelial Cells / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005938:Glucocorticoids / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013256:Steroids / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology; D014684:Venae Cavae / Q000201:enzymology / Q000378:metabolism
D015415:Biomarkers; D016895:Culture Media, Serum-Free; D005938:Glucocorticoids; D007527:Isoenzymes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D013256:Steroids; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C468386:HSD11B1 protein, human; C468387:HSD11B2 protein, human