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Supplementary Materials to Type I interferons modulate vascular function, repair, thrombosis and plaque progression in murine models of lupus and atherosclerosis

dc.contributor.authorThacker SG, Zhao W, Smith CK, Luo W, Wang H, Vivekanandan-Giri A, Rabquer BJ, Koch AE, Pennathur S, Davidson A, Eitzman DT, Kaplan MJ.
dc.date.accessioned2012-08-21T18:54:18Z
dc.date.available2012-08-21T18:54:18Z
dc.date.issued2012-08-21
dc.identifier.citationArthritis Rheum. 2012 May 1. doi: 10.1002/art.34504. [Epub ahead of print] <http://hdl.handle.net/2027.42/92474>en_US
dc.identifier.urihttps://hdl.handle.net/2027.42/92474
dc.description2 supplementary figures and 1 table to go with published manuscript.en_US
dc.description.abstractAbstract OBJECTIVES: Patients with systemic lupus erythematosus (SLE) have a striking increase in atherothromboticcardiovascular disease (CVD), not explained by the Framingham risk equation. In vitrostudies indicate that type-I Interferons (IFNs) may play prominent roles in increased CV risk in SLE. However, the in vivo relevance of these findings, with regards to the development of CVD, has not been characterized. We examinedthe role of type-I IFNs in endothelial dysfunction, aberrant vascular repair, and atherothrombosis in murine models of lupus and atherosclerosis. METHODS: Lupus-prone New Zealand Mixed-2328 mice (NZM) and atherosclerosis-prone Apolipoprotein-E-knockout mice (ApoE-/-) were compared to mice lacking type-I IFN-receptor (INZM and ApoEIFNR-/-, respectively) in their endothelial vasodilatory function, endothelial progenitor cell (EPC)function, in vivoneoangiogenesis, plaque development and occlusive thrombosis. Similar experiments were performed when NZM and ApoE-/- received an IFN-α-containing or an empty adenovirus. RESULTS: Loss of type I-IFN-receptor signaling improves endothelium-dependent vasorelaxation, lipoprotein parameters, EPC numbers and function and neoangiogenesis in lupus-prone mice, independent of disease activity or gender. Further, acute exposure to IFN-α impairs endothelial vasorelaxation and EPC function in lupus-prone and non-lupus-prone mice. ApoEIFNR-/- mice have decreased atherosclerosis severity and arterialinflammatory infiltratesand increased neoangiogenesis, compared to ApoE-/- mice, whileNZM and ApoE(-/-) mice exposed to IFN-αdevelop accelerated thrombosis and platelet activation. CONCLUSIONS: These results support the hypothesis that type I-IFNs play key roles in the development of premature CVD in SLE and, potentially, in the general population, through pleiotropic deleterious effects on the vasculature. Copyright © 2012 by the American College of Rheumatologyen_US
dc.language.isoen_USen_US
dc.subjectMurine Modelsen_US
dc.subjectSystemic Lupus Erythematosusen_US
dc.subjectAtherosclerosisen_US
dc.subjectType 1 Interferonsen_US
dc.subjectThrombosisen_US
dc.subjectPlaque Progressionen_US
dc.subjectCardiovascular Diseaseen_US
dc.titleSupplementary Materials to Type I interferons modulate vascular function, repair, thrombosis and plaque progression in murine models of lupus and atherosclerosisen_US
dc.title.alternativeSupplementary Materialsen_US
dc.typeImageen_US
dc.typeOtheren_US
dc.subject.hlbsecondlevelInternal Medicine and Specialties
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Revieweden_US
dc.contributor.affiliationumDept of Internal Medicine, Division of Rheumatologyen_US
dc.contributor.affiliationumcampusAnn Arboren_US
dc.identifier.pmid22549550
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/92474/1/Kaplan_Supplements Arth & Rheum 2012 Thacker et al.pdf
dc.owningcollnameRheumatology, Division of


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