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dc.contributor.authorTsiantoulas, Dimitriosen
dc.contributor.authorBot, Ilzeen
dc.contributor.authorOzsvar-Kozma, Mariaen
dc.contributor.authorGöderle, Lauraen
dc.contributor.authorPerkmann, Thomasen
dc.contributor.authorHartvigsen, Karstenen
dc.contributor.authorConrad, Daniel Hen
dc.contributor.authorKuiper, Johanen
dc.contributor.authorMallat, Ziaden
dc.contributor.authorBinder, Christoph Jen
dc.date.accessioned2019-04-24T09:25:26Z
dc.date.available2019-04-24T09:25:26Z
dc.date.issued2017-01en
dc.identifier.issn0009-7330
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/291930
dc.description.abstractRATIONALE: Deficiency of secreted IgM (sIgM-/-) accelerates atherosclerosis in Ldlr-/-mice. Several atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing inflammation induced by oxidized low-density lipoprotein and promoting apoptotic cell clearance. However, the mechanisms by which the lack of sIgM promotes lesion formation remain unknown. OBJECTIVE: To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice. METHODS AND RESULTS: We here show that both sIgM-/- and Ldlr-/-sIgM-/- mice develop increased plasma IgE titers because of impaired generation of B cells expressing the low-affinity IgE receptor CD23, which mediates the clearance of IgE antibodies. We further report that Ldlr-/-sIgM-/- mice exhibit increased numbers of activated mast cells and neutrophils in the perivascular area of atherosclerotic plaques. Treatment with an anti-IgE-neutralizing antibody fully reversed vascular inflammation and accelerated atherosclerotic lesion formation in cholesterol-fed Ldlr-/-sIgM-/- mice. CONCLUSIONS: Thus, our data identify a previously unsuspected mechanism by which sIgM deficiency aggravates atherosclerosis.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherLippincott Williams & Wilkins Ltd.
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectMice, Knockouten
dc.subjectMiceen
dc.subjectImmunoglobulin Een
dc.subjectImmunoglobulin Men
dc.subjectMaleen
dc.subjectAtherosclerosisen
dc.subjectMice, 129 Strainen
dc.subjectBiomarkersen
dc.titleIncreased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency.en
dc.typeArticle
prism.endingPage84
prism.issueIdentifier1en
prism.publicationDate2017en
prism.publicationNameCirculation researchen
prism.startingPage78
prism.volume120en
dc.identifier.doi10.17863/CAM.24623
dcterms.dateAccepted2016-11-30en
rioxxterms.versionofrecord10.1161/circresaha.116.309606en
rioxxterms.versionAM*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2017-01en
dc.contributor.orcidTsiantoulas, Dimitrios [0000-0002-7743-3192]
dc.contributor.orcidBot, Ilze [0000-0002-1242-1959]
dc.contributor.orcidPerkmann, Thomas [0000-0002-7976-0285]
dc.contributor.orcidMallat, Ziad [0000-0003-0443-7878]
dc.contributor.orcidBinder, Christoph J [0000-0001-8313-7050]
dc.identifier.eissn1524-4571
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBritish Heart Foundation (RG/10/001/27643)


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