VASCULAR BIOLOGY (RS ROSENSON, SECTION EDITOR) Modulation of 11β-Hydroxysteroid Dehydrogenase as a Strategy to Reduce Vascular Inflammation

# The Author(s) 2013. This article is published with open access at Springerlink.com Abstract Atherosclerosis is a chronic inflammatory disease in which initial vascular damage leads to extensive macro-phage and lymphocyte infiltration. Although acutely gluco-corticoids suppress inflammation, chronic glucocorticoid excess worsens atherosclerosis, possibly by exacerbating systemic cardiovascular risk factors. However, glucocorti-coid action within the lesion may reduce neointimal prolif-eration and inflammation. Glucocorticoid levels within cells do not necessarily reflect circulating levels due to pre-receptor metabolism by 11β-hydroxysteroid dehydroge-nases (11β-HSDs). 11β-HSD2 converts active glucocorti-coids into inert 11-keto forms. 11β-HSD1 catalyses the reverse reaction, regenerating active glucocorticoids. 11β-HSD2-deficiency / inhibition causes hypertension, whereas deficiency / inhibition of 11β-HSD1 generates a cardioprotective lipid profile and improves glycemic control. Importantly, 11β-HSD1-deficiency / inhibition is atheroprotective, whereas 11β-HSD2-deficiency acceler-ates atherosclerosis. These effects are largely independent of systemic risk factors, reflecting modulation of gluco-corticoid action and inflammation within the vasculature. Here, we consider whether evidence linking the 11β-HSDs to vascular inflammation suggests these isozymes are potential therapeutic targets in vascular injury and atherosclerosis