{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:36:52Z","timestamp":1792233412556,"version":"4.4.0"},"reference-count":90,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T00:00:00Z","timestamp":1765929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["2407 [360043781]"],"award-info":[{"award-number":["2407 [360043781]"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR259 [397484323]"],"award-info":[{"award-number":["TRR259 [397484323]"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009983","name":"Center for Molecular Medicine Cologne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009983","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Neven-DuMont Foundation"},{"name":"La Caixa Banking Foundation","award":["HR18-00068"],"award-info":[{"award-number":["HR18-00068"]}]},{"name":"La Caixa Banking Foundation","award":["PID2020-115217RB-I00"],"award-info":[{"award-number":["PID2020-115217RB-I00"]}]},{"name":"La Caixa Banking Foundation","award":["PID2021-122388OB-I00"],"award-info":[{"award-number":["PID2021-122388OB-I00"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["CB16\/11\/00264"],"award-info":[{"award-number":["CB16\/11\/00264"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Patients suffering from Marfan syndrome (MFS), the most prevalent inherited connective tissue disorder, face premature mortality due to dissection and rupture of thoracic aortic aneurysms. Here, we questioned whether myeloperoxidase (MPO), a leucocyte-derived enzyme with high affinity to the vessel wall, contributes to aortic remodelling in MFS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Plasma MPO levels were evaluated in MFS patients and healthy controls. Thoracic aortic aneurysm formation was determined in heterozygous transgenic Fbn1C1041G\/+ (MFS) mice, MPO-deficient MFS mice (MFSxMpo\u2212\/\u2212), and MFS mice treated with an MPO inhibitor by ultrasound and histology.<\/jats:p>\n                    <jats:p>MFS patients exhibited increased circulating MPO levels and marked aortic MPO deposition. In MFS mice, MPO-deficiency reduced aortic elastin fragmentation and aneurysm formation. RNA sequencing revealed an inflammatory gene program in aortic endothelial cells isolated from MFS mice in comparison to WT and MFSxMpo\u2212\/\u2212 mice. This was accompanied by enhanced endothelial expression of the leucocyte adhesion molecule ICAM-1, increased leucocyte adhesion, and, consequently, leucocyte infiltration in MFS aortae. Moreover, MPO directly contributed to adverse extracellular matrix remodelling through overproduction of reactive oxygen species and subsequent vascular protein modifications leading to enhanced matrix metalloproteinase 2\/9 activity. Lastly, treatment of MFS mice with the orally available MPO inhibitor AZM198 attenuated TAA formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MPO is increased in MFS and contributes to thoracic aortic dilatation by inducing inflammatory endothelial activation, oxidative stress, and adverse extracellular matrix remodelling. Pharmacological and genetic inhibition of MPO reduced MFS-related aortic dilation in mice, highlighting MPO as a promising therapeutic target in MFS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf248","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:01:12Z","timestamp":1764162072000},"page":"230-244","source":"Crossref","is-referenced-by-count":7,"title":["Myeloperoxidase aggravates thoracic aortic aneurysm formation in Marfan disease"],"prefix":"10.1093","volume":"122","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8578-0290","authenticated-orcid":false,"given":"Dennis","family":"Mehrkens","sequence":"first","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Dohr","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix Sebastian","family":"Nettersheim","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Ballmann","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jil","family":"Bastigkeit","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Br\u00fcckner","sequence":"additional","affiliation":[{"name":"Life and Brain Center, Medical Faculty, Institute of Physiology I, University of Bonn , Bonn 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,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Francisco","family":"Nistal","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"Cardiovascular Surgery, Facultad de Medicina, University Hospital Marqu\u00e9s de Valdecilla-IDIVAL, Universidad de Cantabria , Santander ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel R","family":"Campanero","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV) , Madrid ,","place":["Spain"]},{"name":"Cell-Cell Communication & Inflammation Unit, Centro de Biolog\u00eda Molecular Severo Ochoa (CBMSO), Consejo Superior de Investigaciones Cient\u00edficas\u2013Universidad Aut\u00f3noma de Madrid , Madrid 28049 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