{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:17:51Z","timestamp":1761862671611},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,3,28]],"date-time":"2007-03-28T00:00:00Z","timestamp":1175040000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Mixed cryoglobulinemia (MC) is a systemic vasculitis, usually associated with hepatitis C virus (HCV) infection. The molecular mechanisms responsible for HCV\u2010associated MC (HCV\u2010MC) 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\u2010MC vasculitis, patients with polyarteritis nodosa (PAN), and patients with noninflammatory idiopathic neuropathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The quantitative expression levels of 42 selected genes involved in inflammatory vascular damage were assessed in nerve lesions of patients with HCV\u2010MC vasculitis, PAN (rheumatic disease controls), and noninflammatory idiopathic neuropathy (noninflammatory neuropathy controls), using real\u2010time reverse transcriptase\u2013polymerase chain reaction. Genes were considered to be differentially expressed when there was a &gt;2\u2010fold difference in mean expression levels between groups and the <jats:italic>P<\/jats:italic> value was less than 0.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Expression levels of 8 genes were significantly increased in HCV\u2010MC 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\u2010MC patients had higher expression levels of genes encoding oxidative stress\u2013derived molecules (MT1H, endothelial cell nitric oxide synthase 3, Hsp70, and Hsp90) and tissue plasminogen activator and lower expression levels of matrix metalloproteinase 7 (MMP\u20107). HCV\u2010MC neuropathies were classified according to their morphologic pattern and the presence or absence of necrotizing arteritis. MMP\u20101, MMP\u20107, MMP\u20109, and interleukin\u20101\u03b2 were up\u2010regulated in patients with necrotizing arteritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This comprehensive molecular study of HCV\u2010MC vasculitis provides strong evidence that MMPs, proinflammatory cytokines, and oxidative stress\u2013derived molecules have a role in the pathogenesis of HCV\u2010MC vasculitis neuropathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22456","type":"journal-article","created":{"date-parts":[[2007,3,28]],"date-time":"2007-03-28T17:52:19Z","timestamp":1175104339000},"page":"1315-1324","source":"Crossref","is-referenced-by-count":26,"title":["Role of matrix metalloproteinases, proinflammatory cytokines, and oxidative stress\u2013derived molecules in hepatitis C virus\u2013associated mixed cryoglobulinemia vasculitis 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