Oct 29:  TRalpha protects against atherosclerosis: identification of a novel anti-inflammatory inflammasome-dependent property for TRalpha in mice

Speaker：Karine Gauthier Vanacker

Host: Pro. Jiemin Wong

When: 2013-10-29  13:30

Where: Conference Room 534, School of Life Sciences

Abstract: Hypothyroidism is associated with an increased occurrence of atherosclerosis suggesting some protective role for thyroid hormones usually attributed to cholesterol lowering by TR. Here TR was shown to also slow down the progression of the disease. Introduction of TR mutation in the ApoE-/- background accelerated the appearance of plaques. Earlier cholesterol accumulation was detected in aorta macrophages likely due to impaired cholesterol efflux. The IL-1b inflammatory cytokine was elevated in serum and macrophages in correlation with an activation of the AKT/NF-kB pathway in these cells. Inhibition of AKT or IL-1b signaling, and genetic invalidation of the inflammasome pathway, prevented inflammation and restored normal cholesterol efflux. The absence of TRa increased inflammasome activity, leading to IL-1b secretion, activation of IL-1R and to the downstream AKT/NF-kB pathway. Thus TR protects against atherosclerosis by limiting inflammation that in turn avoids cholesterol accumulation. This activity should be relevant for other inflammatory pathologies.