{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:18:11Z","timestamp":1790036291758,"version":"4.0.1"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,27]],"date-time":"2012-07-27T00:00:00Z","timestamp":1343347200000},"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":[[2012,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Although the accelerating effect of systemic lupus erythematosus (SLE) on atherosclerosis is well established, the underlying mechanisms are unknown. The aim of this study was to explore the hypothesis that lupus autoimmunity modulates the effect of hypercholesterolemia in driving arterial pathologic development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Low\u2010density lipoprotein receptor\u2013deficient (<jats:italic>Ldlr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>) mice were crossed with B6.129\u2010<jats:italic>Sle16<\/jats:italic> (<jats:italic>Sle16<\/jats:italic>)\u2013congenic autoimmune mice to obtain <jats:italic>Sle16. Ldlr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, which were compared with <jats:italic>Ldlr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Sle16<\/jats:italic> control mice. All mice were fed either a low\u2010fat or high\u2010fat diet. Groups of mice were compared, by strain and by diet group, for features of accelerated atherosclerosis and autoimmunity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Presence of the <jats:italic>Sle16<\/jats:italic> locus significantly increased the extent of atherosclerosis in <jats:italic>Ldlr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Circulating C3 levels were significantly reduced in <jats:italic>Sle16.Ldlr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice compared to <jats:italic>Ldlr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> control mice and this was paralleled by a marked reduction in arterial lesion C3 deposition despite similar levels of IgG deposition between the groups. Increased numbers of apoptotic cells in plaques were observed in the high\u2010fat\u2013fed <jats:italic>Sle16.Ldlr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice, consistent with the observed defective clearance of cellular debris. After receiving the high\u2010fat diet, <jats:italic>Sle16.Ldlr<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice developed glomerulonephritis and displayed enhanced glomerular C3 deposition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results indicate that accelerated atherosclerosis and renal inflammation in SLE are closely linked via immune complex formation and systemic complement depletion. However, whereas hyperlipidemia will enhance renal immune complex\u2013mediated complement activation and the development of nephritis, accelerated atherosclerosis is, instead, related to complement depletion and a reduction in the uptake of apoptotic\/necrotic debris. These results suggest that aggressive treatment of hyperlipidemia in patients with SLE may reduce the occurrence of lupus nephritis, as well as diminish the risk of accelerated atherosclerosis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.34451","type":"journal-article","created":{"date-parts":[[2012,3,6]],"date-time":"2012-03-06T01:27:26Z","timestamp":1330997246000},"page":"2707-2718","source":"Crossref","is-referenced-by-count":23,"title":["Distinct roles for complement in glomerulonephritis and atherosclerosis revealed in mice with a combination of lupus and hyperlipidemia"],"prefix":"10.1002","volume":"64","author":[{"given":"Myles J.","family":"Lewis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talat H.","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliane","family":"Fossati\u2010Jimack","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Carassiti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. 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