title: Oxidative Stress and Upregulation of Antioxidant Proteins, Including Adiponectin, in Extraocular Muscular Cells, Orbital Adipocytes, and Thyrocytes in Graves' Disease Associated with Orbitopathy.
abstract: BACKGROUND
  Graves' orbitopathy (GO) is the main extrathyroidal manifestation associated with Graves' disease (GD). It is characterized by reduced eye motility due to an increased volume of orbital fat and/or of extraocular muscles (EOMs) infiltrated by fibrosis and adipose tissue. The pathogenetic mechanisms leading to fibrosis and adipogenesis are mainly based on the interaction between orbital fibroblasts and immune cells (lymphocytes and mast cells) infiltrating the GO EOMs.
  
  
  METHODS
  Analysis of the morphological status, oxidative stress (OS), and antioxidant defenses in the orbital muscular cells and adipocytes in GO patients compared with controls was conducted.
  
  
  RESULTS
  Both cell types are affected by OS, as shown by the increased expression of 4-hydroxynonenal, which leads to apoptosis in muscular cells. However, the EOMs and the adipocytes possess antioxidant defenses (peroxiredoxin 5 and catalase) against the OS, which are also upregulated in thyrocytes in GD. The expression of adiponectin (ApN) and proliferator-activated receptor gamma (PPARγ) is also increased in GO muscular cells and adipocytes. OS and antioxidant proteins expression are correlated to the level of blood antithyrotropin receptor antibodies (TSHR-Ab).
  
  
  CONCLUSIONS
  Even when TSHR-Ab level is normalized, OS and antioxidant protein expression is high in EOM muscular cells and adipocytes in GO compared with controls. This justifies a supplementation with antioxidants in active as well as chronic GO patients. Orbital muscular cells are also the sources of PPARγ and ApN, which have direct or indirect local protective effects against OS. Modulation of these proteins could be considered as a future therapeutic approach for GO.
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Lancelot
authors.initials: L
authors.lastname: Marique
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Maximin
authors.initials: M
authors.lastname: Senou
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Julie
authors.initials: J
authors.lastname: Craps
authors.affiliation: 2 Pôles d'Endocrinologie, Diabète, et Nutrition, Institut de recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Aurélie
authors.initials: A
authors.lastname: Delaigle
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Elliott
authors.initials: E
authors.lastname: Van Regemorter
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Alexis
authors.initials: A
authors.lastname: Wérion
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Victoria
authors.initials: V
authors.lastname: Van Regemorter
authors.affiliation: 3 Département de Chirurgie Endocrinienne et de Trasplantation rénale, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Michel
authors.initials: M
authors.lastname: Mourad
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Catherine
authors.initials: C
authors.lastname: Nyssen-Behets
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Benoit
authors.initials: B
authors.lastname: Lengelé
authors.affiliation: 4 Département d'Ophtalmologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Lelio
authors.initials: L
authors.lastname: Baldeschi
authors.affiliation: 4 Département d'Ophtalmologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Antonella
authors.initials: A
authors.lastname: Boschi
authors.affiliation: 2 Pôles d'Endocrinologie, Diabète, et Nutrition, Institut de recherche Expérimentale et Clinique, Université Catholique de Louvain , Brussels, Belgium .|5 Département d'Endocrinologie, Secteur des Sciences de la santé, Faculté de Médecine et de Médecine Dentaire, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Sonia
authors.initials: S
authors.lastname: Brichard
authors.affiliation: 5 Département d'Endocrinologie, Secteur des Sciences de la santé, Faculté de Médecine et de Médecine Dentaire, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Chantal
authors.initials: C
authors.lastname: Daumerie
authors.affiliation: 1 Pôles de Morphologie, Université Catholique de Louvain , Brussels, Belgium .
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Many
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D001706:Biopsy; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006111:Graves Disease / Q000378:metabolism*; D049970:Graves Ophthalmopathy / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000166:cytology; D009915:Orbit / Q000473:pathology*; D018384:Oxidative Stress; D047495:PPAR gamma / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000378:metabolism; D013961:Thyroid Gland / Q000166:cytology; D015854:Up-Regulation
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D000975:Antioxidants; D047495:PPAR gamma; D011989:Receptors, Thyrotropin