title: Role of matrix metalloproteinases, proinflammatory cytokines, and oxidative stress-derived molecules in hepatitis C virus-associated mixed cryoglobulinemia vasculitis neuropathy.
abstract: OBJECTIVE
  Mixed cryoglobulinemia (MC) is a systemic vasculitis, usually associated with hepatitis C virus (HCV) infection. The molecular mechanisms responsible for HCV-associated MC (HCV-MC) vasculitis are largely unknown. This study was undertaken to assess the expression profile of selected genes involved in inflammatory vascular damage in patients with HCV-MC vasculitis, patients with polyarteritis nodosa (PAN), and patients with noninflammatory idiopathic neuropathy.
  
  
  METHODS
  The quantitative expression levels of 42 selected genes involved in inflammatory vascular damage were assessed in nerve lesions of patients with HCV-MC vasculitis, PAN (rheumatic disease controls), and noninflammatory idiopathic neuropathy (noninflammatory neuropathy controls), using real-time reverse transcriptase-polymerase chain reaction. Genes were considered to be differentially expressed when there was a >2-fold difference in mean expression levels between groups and the P value was less than 0.05.
  
  
  RESULTS
  Expression levels of 8 genes were significantly increased in HCV-MC patients versus control patients with noninflammatory idiopathic neuropathy, with the highest increase for metallothionein 1 H (MT1H), a hypoxic and oxidative stress protein. Compared with PAN patients, HCV-MC patients had higher expression levels of genes encoding oxidative stress-derived molecules (MT1H, endothelial cell nitric oxide synthase 3, Hsp70, and Hsp90) and tissue plasminogen activator and lower expression levels of matrix metalloproteinase 7 (MMP-7). HCV-MC neuropathies were classified according to their morphologic pattern and the presence or absence of necrotizing arteritis. MMP-1, MMP-7, MMP-9, and interleukin-1beta were up-regulated in patients with necrotizing arteritis.
  
  
  CONCLUSIONS
  This comprehensive molecular study of HCV-MC vasculitis provides strong evidence that MMPs, proinflammatory cytokines, and oxidative stress-derived molecules have a role in the pathogenesis of HCV-MC vasculitis neuropathy.
authors: Université Pierre et Marie Curie-Paris VI, CNRS UMR 7087, and Hôpital Pitié-Salpétrière, Paris, France.
authors: David
authors: D
authors: Saadoun
authors: Ivan
authors: I
authors: Bieche
authors: François-Jérome
authors: FJ
authors: Authier
authors: Ingrid
authors: I
authors: Laurendeau
authors: Florence
authors: F
authors: Jambou
authors: Jean Charles
authors: JC
authors: Piette
authors: Michel
authors: M
authors: Vidaud
authors: Thierry
authors: T
authors: Maisonobe
authors: Patrice
authors: P
authors: Cacoub
mesh_terms: D000328:Adult; D000368:Aged; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D003449:Cryoglobulinemia / Q000378:metabolism / Q000821:virology*; D005260:Female; D020869:Gene Expression Profiling; D050884:HSP72 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006526:Hepatitis C / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000235:genetics* / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics*; D010543:Peroneal Nerve / Q000378:metabolism / Q000473:pathology; D010488:Polyarteritis Nodosa / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011115:Polyneuropathies / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D018925:Chemokines; D050884:HSP72 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D008668:Metallothionein; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D045726:Metalloproteases; D010959:Tissue Plasminogen Activator