title: A review of the effects of statins in systemic sclerosis.
abstract: We performed a literature review assessing possible benefits of statins in systemic sclerosis (SSc).
  
  
  
  PubMed, Embase, Cochrane Databases, and Medline were searched. Full-text English publications were identified in which the effects of statins in SSc were examined. Letters, review articles, and studies on morphea were excluded.
  
  
  
  In all, 18 of 404 studies were relevant. In vitro, statins decreased transcription and translation of IL-6 and collagen, with reversal via mevalonate. Animal studies demonstrated reduced production of Ras (a protein superfamily of GTPases), Rho (part of the Ras superfamily), and extracellular signal-regulated kinases (ERK), less fibrosis and myofibroblast transdifferentiation, and improved macrovasculature. In human studies, IL-6, an inflammatory cytokine, was reduced. Usually endothelial progenitor cell concentrations increased, and flow-mediated dilatation improved. Raynaud's phenomenon, digital ulcers, and physician global assessments improved in the majority of studies of statin treatment in SSc. None of the 256 patients receiving statins experienced transaminitis or myopathy.
  
  
  
  Not all findings were consistent. However, in general, in vitro, animal, and human studies demonstrated benefit in SSc pathophysiology, likely mediated through inhibition of lipid intermediate synthesis. Clinical improvement in SSc circulatory complications was observed. Statins seemed safe and well tolerated in SSc. Larger longer-term multi-site randomized trials are needed to further determine the role of statins as adjunctive treatment of this complex, heterogeneous connective tissue disease.
authors.affiliation: De Groote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Karim
authors.initials: K
authors.lastname: Ladak
authors.affiliation: Schulich School of Medicine, Western University, London, Ontario, Canada; St. Joseph's Health Care, 268 Grosvenor St., London, Ontario, Canada N6A 4V2. Electronic address: janet.pope@sjhc.london.on.ca.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Pope
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects; D003094:Collagen / Q000187:drug effects / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000166:cytology / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D005355:Fibrosis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D058628:Myofibroblasts / Q000187:drug effects; D011928:Raynaud Disease / Q000209:etiology / Q000503:physiopathology; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D012883:Skin Ulcer / Q000209:etiology / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects; D018631:ras Proteins / Q000187:drug effects / Q000378:metabolism
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins
keywords: Animal models; Cytokines; Digital ulcers; Endothelial progenitor cells; Fibroblasts; Hydroxy-methyl-glutaryl-CoA inhibitors; Pleiotropic; Review; Statins; Systemic sclerosis (scleroderma); Trials