Research Article| Volume 191, ISSUE 2, P333-339, April 2007

Atherogenesis takes place in cholesterol-fed rabbits when circulating concentrations of endogenous cortisol are increased and inflammation suppressed


      Atherosclerosis is an inflammatory disease, but the respone of the endogenous anti-inflammatory system during this process has not been evaluated previously. Cortisol is the end product of this anti-inflammatory system, but is also able to activate cellular processes that induce atherogenesis; however, it is unknown whether atherogenesis occurs when circulating concentrations of endogenous cortisol are increased or when they are decreased. We have evaluated the counter-regulatory responses of cortisol and interleukin-1β (IL-1β) during the short- and long-term responses to vascular injury in rabbits fed a 2% cholesterol diet. In the short-term group (n = 18), serum cortisol and IL-1β concentrations were measured after 10, 20 and 30 days. Rabbits developed hypercholesterolemia and hypercortisolemia, with only modest increases in IL-1β. Although inflammation was low-grade, atherogenesis took place, with subintimal lipid accumulation evident on day 30. In the second group (n = 18), we evaluated variables after 40, 60 and 90 days. This group developed hypercholesterolemia, but serum cortisol concentrations were inappropriately normal, while IL-1β concentrations were elevated 8.6-fold; advanced atherosclerotic plaques were evident on days 60 and 90. These results show that atherogenesis occurs when high endogenous cortisol levels are suppressing inflammation, and are consistent with a promotion of early atherogenesis by high cortisol concentrations.


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