title: Propylthiouracil modulates aortic vasculopathy in the oxidative stress model of systemic sclerosis.
abstract: BACKGROUND
  In systemic sclerosis (SSc) vasculopathy affects small arteries and capillaries, but recent evidences show also macrovascular alterations. Experimental data suggest that propylthiouracil (PTU) abrogates the development of cutaneous and pulmonary fibrosis during SSc. The aim of this study was to evaluate the effect of propylthiouracil on aortic lipid peroxidation, intima-media thickness and myofibroblasts differentiation in experimental SSc.
  
  
  METHODS
  SSc was induced in BALB/c mice by daily subcutaneous injections of hypochlorous acid (HOCl) for 6weeks. Mice (n=25) were randomized to receive daily: HOCl (n=10), HOCl+PTU (n=10), or vehicle (n=5). Thoracic aorta was evaluated by histological methods to measure intima-media thickness and by immunostaining for α-smooth muscle actin (α-SMA) to assess myofibroblast differentiation. Aortic and plasma levels of malondialdehyde (MDA) were also measured.
  
  
  RESULTS
  HOCl induced a significant increase in aortic intima-media thickness compared to controls (p<0.001), while PTU administration prevented intima-media thickening (p<0.01). Myofibroblast differentiation was also less evident in HOCl+PTU-treated animals (p<0.05) compared to mice treated with HOCl alone. The increase in aortic and plasma MDA levels induced by HOCl, was significantly prevented by PTU administration (p<0.05).
  
  
  CONCLUSIONS
  PTU, by reducing lipid peroxidation, prevents aortic thickening and myofibroblast differentiation induced by HOCl, reducing macrovascular alterations in experimental SSc.
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. Electronic address: gianbagnato@unime.it.
authors: Gianluca
authors: G
authors: Bagnato
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Alessandra
authors: A
authors: Bitto
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Gabriele
authors: G
authors: Pizzino
authors: Division of Rheumatology, Department of Internal Medicine, University of Louisville, Louisville, KY, USA.
authors: William Neal
authors: WN
authors: Roberts
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Francesco
authors: F
authors: Squadrito
authors: Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, Messina, Italy.
authors: Domenica
authors: D
authors: Altavilla
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Gianfilippo
authors: G
authors: Bagnato
authors: Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
authors: Antonino
authors: A
authors: Saitta
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology / Q000627:therapeutic use; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D011441:Propylthiouracil / Q000494:pharmacology / Q000627:therapeutic use*; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*
chemical_list: D013956:Antithyroid Agents; D011441:Propylthiouracil
keywords: Animal model; Aorta; Lipid peroxidation; Propylthiouracil; Reactive oxygen species; Systemic sclerosis; Thyroid