11-Hydroxysteroid dehydrogenases catalyze interconversion of 11-hydroxy-glucocorticoids with inactive 11-keto metabolites. In blood vessel walls, loss of 11HSD1 is thought to reduce local glucocorticoid concentrations, reducing the progression of atheroma and enhancing angiogenesis. Conversely, on the basis that 11HSD1 is up-regulated 5-fold by inflammatory cytokines in cultured human vascular smooth muscle cells (VSMCs), it has been proposed that increased 11HSD1 during vascular inflammation provides negative feedback suppression of inflammation. We aimed to determine whether inflammation and injury selectively up-regulate 11HSD1 reductase activity in vitro and in vivo in intact vascular tissue in mice.

In isolated mouse aortae and femoral arteries, reductase activity (converting 11-dehydrocorticosterone to corticosterone) was 10-fold higher than dehydrogenase activity, and was entirely accounted for by 11HSD1 since it was abolished in vessels from 11HSD1^-/- mice. Although 11HSD1 activity was up-regulated by pro-inflammatory cytokines in cultured murine aortic smooth muscle cells, no such effect was evident in intact aortic rings in vitro. Moreover, following systemic inflammation induced by intraperitoneal lipopolysaccharide injection, there was only a modest (18%) increase in 11-reductase activity in the aorta and no increase in the perfused hindlimb. Furthermore, in femoral arteries in which neointimal proliferation was induced by intra-luminal injury there was no change in basal 11HSD1 activity or in the sensitivity of 11-HSD1 to cytokine up-regulation.

We conclude that increased generation of glucocorticoids by 11HSD1 in the murine vessel wall is unlikely to contribute to feedback regulation of inflammation.