{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:04:17Z","timestamp":1785751457767,"version":"3.56.0"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Federal Ministry of Education and Research","award":["01EO1003"],"award-info":[{"award-number":["01EO1003"]}]},{"name":"German Federal Ministry of Education and Research","award":["01EO1503"],"award-info":[{"award-number":["01EO1503"]}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["WE4361\/4-1"],"award-info":[{"award-number":["WE4361\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["WE4361\/7-1"],"award-info":[{"award-number":["WE4361\/7-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"German Centre for Cardiovascular Research","doi-asserted-by":"publisher","award":["81Z0710102"],"award-info":[{"award-number":["81Z0710102"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010447","name":"German Centre for Cardiovascular Research","doi-asserted-by":"publisher","award":["961-386261\/733"],"award-info":[{"award-number":["961-386261\/733"]}],"id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004033","name":"Johannes Gutenberg University Mainz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Boehringer Ingelheim and PHILIPS Medical Systems"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Angiotensin II (AngII) causes hypertension and vascular inflammation and is essential in neurohumoral activation promoting the development of heart failure. The role of the adaptor protein myeloid factor of differentiation 88 (MyD88) driving this pathology remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Male C57BL\/6JMyD88\u2212\/\u2212, LysMCre\/wtMyD88LSL\/LSL, LysMCre\/wt, TLR2\u2212\/\u2212, TLR4\u2212\/\u2212, TLR7\u2212\/\u2212, and TLR9\u2212\/\u2212 mice were investigated (1\u2005mg\/AngIIkg\/d for 7 days). Additionally, we performed biodata analyses from a population-based cohort study and human protein network interactome analyses to understand the role of MyD88 in hypertension. MyD88 deficiency attenuated AngII-induced hypertension and endothelial dysfunction in conductance and resistance vessels, surpassing the effect of single TLR deficiencies. Vascular mRNA expression levels of vcam-1, nos2, nox2, cd62L, cd68, ccl2, il12, and il1b and accumulation of CD11b+Ly6Chi inflammatory monocytes and interferon-g+ NK cells were significantly dampened in MyD88\u2212\/\u2212. Vascular protection was conferred by MyD88 deficiency in bone marrow\u2013derived cells. Re-expression of MyD88 in LysMCre\/wtMyD88LSL\/LSL mice restored AngII-induced pathology, revealing that myeloid cells drive vascular dysfunction in a MyD88-dependent manner. Computational analyses of the human protein interactome demonstrated that MyD88 expression significantly associates with proteins encoded by genetic loci associated with blood pressure traits in multiple GWAS. In hypertensive individuals of the Gutenberg Health Study, monocytic MyD88 mRNA expression was associated with prevalent heart failure and all-cause mortality after a median follow-up of 16.5 years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MyD88 promotes AngII-induced vascular dysfunction and arterial hypertension and might serve as both an inflammatory diagnostic marker and a drug target to tackle the risk of death and incident heart failure in hypertensive patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjopen\/oeag031","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T12:49:47Z","timestamp":1772023787000},"source":"Crossref","is-referenced-by-count":1,"title":["MyD88 in myeloid cells drives angiotensin II-induced vascular inflammation, is associated with prevalent heart failure, and predicts all-cause mortality in arterial hypertension"],"prefix":"10.1093","volume":"6","author":[{"given":"Sabine","family":"Wild","sequence":"first","affiliation":[{"name":"Center for Cardiology, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Finger","sequence":"additional","affiliation":[{"name":"Center for Cardiology, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner Site Rhine-Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Schulz","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Aluia","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner Site Rhine-Main ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimena","family":"Bravo","sequence":"additional","affiliation":[{"name":"Institute of Transfusion-Medicine Center, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 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,","place":["Germany"]},{"name":"Institute for Molecular Biology GGmbH , Ackermannweg 4, Mainz 55128 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3542-6672","authenticated-orcid":false,"given":"Voahanginirina","family":"Randriamboavonjy","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner Site Rhine-Main ,","place":["Germany"]},{"name":"Institute for Vascular Signaling, Centre for Molecular Medicine, Goethe University , Theodor-Stern-Kai 7, Frankfurt am Main 60596 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1446-8101","authenticated-orcid":false,"given":"Johannes","family":"Wild","sequence":"additional","affiliation":[{"name":"Center for Cardiology, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"Center for Thrombosis and Hemostasis 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\u00a0","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3379-2641","authenticated-orcid":false,"given":"Tanja","family":"Zeller","sequence":"additional","affiliation":[{"name":"Institute for Cardiogenetics, University Hospital Schleswig Holstein, University of Luebeck , Ratzeburger Allee 160, L\u00fcbeck 23562 \u00a0","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK), Partner Site Hamburg\/Kiel\/Luebeck ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Gieswinkel","sequence":"additional","affiliation":[{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner Site Rhine-Main ,","place":["Germany"]},{"name":"Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center 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Transfusion-Medicine Center, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"Research Center for Immunotherapy (FZI), University Medical Center, University of Mainz , Langenbeckstr. 1, 55131 Mainz ,","place":["Germany"]},{"name":"German Cancer Research Center (DKFZ) , Im Neuenheimer Feld 280, 69120 Heidelberg ,","place":["Germany"]},{"name":"German Cancer Consortium (DKTK) ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A","family":"Andrade-Navarro","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Johannes Gutenberg University Mainz , Gresemundweg 2, Mainz 55128 ,","place":["Germany"]},{"name":"Institute for Molecular Biology GGmbH , Ackermannweg 4, Mainz 55128 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Wild","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner Site Rhine-Main ,","place":["Germany"]},{"name":"Preventive Cardiology and Preventive Medicine, Center for Cardiology, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5397-2781","authenticated-orcid":false,"given":"Philip","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Center for Cardiology, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz , Langenbeckstrasse 1, Mainz 55131 ,","place":["Germany"]},{"name":"German Center for Cardiovascular Research (DZHK)\u2014Partner Site Rhine-Main ,","place":["Germany"]},{"name":"Medical Clinic I - Cardiology and Internal Intensive Care Medicine, Klinikum Darmstadt GmbH , Grafenstrasse 9, Darmstadt 64283"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,27]]},"reference":[{"key":"2026061208353987500_oeag031-B1","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1084\/jem.20070657","article-title":"Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction","volume":"204","author":"Guzik","year":"2007","journal-title":"J Exp Med"},{"key":"2026061208353987500_oeag031-B2","doi-asserted-by":"crossref","first-page":"2529","DOI":"10.1161\/CIRCULATIONAHA.109.930446","article-title":"Inhibition and genetic ablation of the B7\/CD28 T-cell costimulation axis prevents experimental 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