{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T22:28:41Z","timestamp":1780352921773,"version":"3.54.1"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>The mechanisms underlying formation of arterial aneurysms remain incompletely understood. Because inflammation is a common feature during the progressive degeneration of the aortic wall, we studied the role of the costimulatory molecule CD40L, a major driver of inflammation, in aneurysm formation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Transcriptomics data obtained from human abdominal aortic aneurysms and normal aortas revealed increased abundance of both CD40L and CD40 in media of thrombus-free and thrombus-covered human abdominal aortic aneurysms samples. To further unravel the role of CD40L in aneurysm formation, apolipoprotein E\u2013deficient (\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              ) and\n              <jats:italic>Cd40l<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice were infused with angiotensin II for 7 and 28 days. Only a minority of\n              <jats:italic>Cd40l<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice (33% and 17%) developed (dissecting) aneurysms compared with 75% and 67% of\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              littermates after 7 and 28 days of infusion, respectively. Total vessel area of the aorta at the suprarenal level was 52% smaller in angiotensin II\u2013infused\n              <jats:italic>Cd40l<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice compared with that in angiotensin II\u2013infused\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice. Chimeric\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice repopulated with\n              <jats:italic>Cd40l<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              bone marrow afforded a similar protection against dissecting aneurysm formation. Moreover, lack of CD40L protected mice from fatal aneurysm rupture. T helper cell and macrophage accumulation in aneurysmal tissue was reduced in\n              <jats:italic>Cd40l<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice with a concomitant decrease in expression of proinflammatory chemo- and cytokines. In addition, aneurysms of\n              <jats:italic>Cd40l<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              <jats:italic>Apoe<\/jats:italic>\n              <jats:sup>\u2212\/\u2212<\/jats:sup>\n              mice displayed reduced abundance of matrix metalloproteinase-13 and an increase in tissue inhibitor of metalloproteinase-3 while activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 was diminished.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Deficiency of (hematopoietic) CD40L protects against dissecting aneurysm formation and reduces the incidence of fatal rupture. This is associated with a decreased accumulation and activation of inflammatory cells and a dampened protease activity in the arterial wall.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.117.310640","type":"journal-article","created":{"date-parts":[[2018,3,9]],"date-time":"2018-03-09T10:47:10Z","timestamp":1520592430000},"page":"1076-1085","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":26,"title":["CD40L Deficiency Protects Against Aneurysm Formation"],"prefix":"10.1161","volume":"38","author":[{"given":"Pascal J.H.","family":"Kusters","sequence":"first","affiliation":[{"name":"From the Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (P.J.H.K., T.T.P.S., L.B., D.L., H.W., V.d.W., E.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom T.P.","family":"Seijkens","sequence":"additional","affiliation":[{"name":"From the Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (P.J.H.K., T.T.P.S., L.B., D.L., H.W., V.d.W., E.L.)"},{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University, Munich, Germany (T.T.P.S., D.L., H.W., N.G., E.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Beckers","sequence":"additional","affiliation":[{"name":"From the Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (P.J.H.K., T.T.P.S., L.B., D.L., H.W., V.d.W., E.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Lievens","sequence":"additional","affiliation":[{"name":"From the Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (P.J.H.K., T.T.P.S., L.B., D.L., H.W., V.d.W., E.L.)"},{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University, Munich, Germany (T.T.P.S., D.L., H.W., N.G., E.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Winkels","sequence":"additional","affiliation":[{"name":"From the Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (P.J.H.K., T.T.P.S., L.B., D.L., H.W., V.d.W., E.L.)"},{"name":"Institute for Cardiovascular Prevention (IPEK), Ludwig-Maximilians University, Munich, Germany (T.T.P.S., D.L., H.W., N.G., E.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"de Waard","sequence":"additional","affiliation":[{"name":"From the Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands (P.J.H.K., T.T.P.S., L.B., D.L., H.W., V.d.W., E.L.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan","family":"Duijvestijn","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Maastricht, The Netherlands 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