{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T01:59:50Z","timestamp":1777946390416,"version":"3.51.4"},"reference-count":50,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2012,11,28]],"date-time":"2012-11-28T00:00:00Z","timestamp":1354060800000},"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":[[2012,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Many different genes or mediators have been implicated in promoting the development of vasculitis, although little is known regarding the mechanisms that normally act to suppress lesion formation. Endothelial nitric oxide synthase (eNOS) has been shown to inhibit vascular inflammation in many different model systems, but its roles in the pathogenesis of vasculitis have not been elucidated. This study was undertaken to determine the functions of eNOS in the initiation and progression of vasculitic lesion formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>MRL\/MpJ\u2010<jats:italic>Fas<\/jats:italic><jats:sup><jats:italic>lpr<\/jats:italic><\/jats:sup> mice lacking the gene for eNOS (<jats:italic>Nos3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) were generated and comprehensively evaluated and compared to controls with regard to the development of autoimmune disease, including vasculitic lesion formation and glomerulonephritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>Nos3<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup> MRL\/MpJ\u2010<jats:italic>Fas<\/jats:italic><jats:sup><jats:italic>lpr<\/jats:italic><\/jats:sup> mice exhibited accelerated onset and increased incidence of renal vasculitis compared to <jats:italic>Nos3<\/jats:italic><jats:sup><jats:italic>+\/+<\/jats:italic><\/jats:sup> controls. In contrast, no significant differences in severity of glomerulonephritis were observed between groups. Vasculitis was also observed in other organs of eNOS\u2010deficient mice, including in the lungs of several of these animals. Ultrastructural analyses of renal lesions revealed the presence of electron\u2010dense deposits in affected arteries, and IgG, IgA, and C3 deposition was observed in some vessels in the kidneys of <jats:italic>Nos3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. In addition, <jats:italic>Nos3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> MRL\/MpJ\u2010<jats:italic>Fas<\/jats:italic><jats:sup><jats:italic>lp<\/jats:italic><\/jats:sup> mice showed increased levels of circulating IgG\u2013IgA immune complexes at 20 weeks of age, compared to <jats:italic>Nos3<\/jats:italic><jats:sup>+\/+<\/jats:sup> MRL\/MpJ\u2010<jats:italic>Fas<\/jats:italic><jats:sup><jats:italic>lpr<\/jats:italic><\/jats:sup> and <jats:italic>Nos3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> C57BL\/6 mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings strongly indicate that eNOS serves as a negative regulator of vasculitis in MRL\/MpJ\u2010<jats:italic>Fas<\/jats:italic><jats:sup><jats:italic>lpr<\/jats:italic><\/jats:sup> mice and further suggest that NO produced by this enzyme may be critical for inhibiting lesion formation and vascular damage in human vasculitic diseases.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.37683","type":"journal-article","created":{"date-parts":[[2012,8,29]],"date-time":"2012-08-29T20:17:53Z","timestamp":1346271473000},"page":"4114-4124","source":"Crossref","is-referenced-by-count":7,"title":["Endothelial nitric oxide synthase inhibits the development of autoimmune\u2010mediated vasculitis in mice"],"prefix":"10.1002","volume":"64","author":[{"given":"Trenton R.","family":"Schoeb","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tambi","family":"Jarmi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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