{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:57:28Z","timestamp":1789019848745,"version":"build-2803163510"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["91739303"],"award-info":[{"award-number":["91739303"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81670413"],"award-info":[{"award-number":["81670413"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["31872787"],"award-info":[{"award-number":["31872787"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation","doi-asserted-by":"crossref","award":["81770445"],"award-info":[{"award-number":["81770445"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Peking University Medicine Seed Fund for Interdisciplinary Research","award":["BMU2018MXU002"],"award-info":[{"award-number":["BMU2018MXU002"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Overactivated B cells secrete pathological antibodies, which in turn accelerate the formation of abdominal aortic aneurysms (AAAs). Hyperhomocysteinaemia (HHcy) aggravates AAA in mice; however, the underlying mechanisms remain largely elusive. In this study, we further investigated whether homocysteine (Hcy)-activated B cells produce antigen-specific antibodies that ultimately contribute to AAA formation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>ELISA assays showed that HHcy induced the secretion of anti-beta 2 glycoprotein I (anti-\u03b22GPI) antibody from B cells both in vitro and in vivo. Mechanistically, Hcy increased the accumulation of various lipid metabolites in B cells tested by liquid chromatography-tandem mass spectrometry, which contributed to elevated anti-\u03b22GPI IgG secretion. By using the toll-like receptor 4 (TLR4)-specific inhibitor TAK-242 or TLR4-deficient macrophages, we found that culture supernatants from Hcy-activated B cells and HHcy plasma IgG polarized inflammatory macrophages in a TLR4-dependent manner. In addition, HHcy markedly increased the incidence of elastase- and CaPO4-induced AAA in male BALB\/c mice, which was prevented in \u03bcMT mice. To further determine the importance of IgG in HHcy-aggravated AAA formation, we purified plasma IgG from HHcy or control mice and then transferred the IgG into \u03bcMT mice, which were subsequently subjected to elastase- or CaPO4-induced AAA. Compared with \u03bcMT mice that received plasma IgG from control mice, \u03bcMT mice that received HHcy plasma IgG developed significantly exacerbated elastase- or CaPO4-induced AAA accompanied by increased elastin degradation, MMP2\/9 expression, and anti-\u03b22GPI IgG deposition in vascular lesions, as shown by immunofluorescence histochemical staining.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our findings reveal a novel mechanism by which Hcy-induced B cell-derived pathogenic anti-\u03b22GPI IgG might, at least in part, contribute to HHcy-aggravated chronic vascular inflammation and AAA formation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvz288","type":"journal-article","created":{"date-parts":[[2019,11,27]],"date-time":"2019-11-27T12:12:17Z","timestamp":1574856737000},"page":"1897-1909","source":"Crossref","is-referenced-by-count":26,"title":["B 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