title: TRα protects against atherosclerosis in male mice: identification of a novel anti-inflammatory property for TRα in mice.
abstract: Hypothyroidism is associated with an increased occurrence of atherosclerosis, suggesting some protective role for thyroid hormones (THs). Hypercholesterolemia is one of the major risk factor to develop this disease. Here, we show that the well-known TH cholesterol lowering effect was dependent on TH nuclear receptor (TR)β liver activity. But most importantly, TRα was also shown to contribute of slowing down atherosclerosis progression via an independent mechanism. Introduction of TRα(0/0) deletion 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-1β inflammatory cytokine was elevated in serum and macrophages in correlation with an activation of the AKT/nuclear factor κB pathway in these cells. Inhibition of AKT prevented inflammation and restored normal cholesterol efflux. Similar low-grade inflammation was identified in TRα(0/0) male mice. Thus, the mere absence of TRα is associated with elevated levels of cytokines likely responsible for cholesterol accumulation and atherosclerosis. This TRα protective activity should be relevant for other inflammatory pathologies.
authors.affiliation: Institut de Génomique Fonctionnelle de Lyon (C.B., L.C., A.D., J.S., K.G.), Université de Lyon, Université Lyon 1, Centre National de la Recherche Scientifique. Institut National de la Recherche Agronomique, Ecole Normale Supérieure de Lyon, 69364 Lyon, France; Inserm Unité 1011 (S.F., D.D.), University of Lille Nord de France and Institut Pasteur de Lille, 59000 Lille, France; and Inserm Equipe Région-Inserm 22/Equipe Associée 4173 (M.B.) and Anira-ANIPHY (P.d.C.), Faculté Rockefeller, Université Lyon 1, 69008 Lyon, France.
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Billon
authors.forename: Laurence
authors.initials: L
authors.lastname: Canaple
authors.forename: Sébastien
authors.initials: S
authors.lastname: Fleury
authors.forename: Alexandre
authors.initials: A
authors.lastname: Deloire
authors.forename: Michel
authors.initials: M
authors.lastname: Beylot
authors.forename: David
authors.initials: D
authors.lastname: Dombrowicz
authors.forename: Peggy
authors.initials: P
authors.lastname: Del Carmine
authors.forename: Jacques
authors.initials: J
authors.lastname: Samarut
authors.forename: Karine
authors.initials: K
authors.lastname: Gauthier
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D016026:Bone Marrow Transplantation / Q000379:methods; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037021:Thyroid Hormone Receptors alpha / Q000172:deficiency / Q000235:genetics*; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D053583:Interleukin-1beta; D016328:NF-kappa B; D037021:Thyroid Hormone Receptors alpha; D013963:Thyroid Hormones; D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt