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Cologne","doi-asserted-by":"publisher","award":["363\/2020"],"award-info":[{"award-number":["363\/2020"]}],"id":[{"id":"10.13039\/501100009983","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009983","name":"Center for Molecular Medicine Cologne, University of Cologne","doi-asserted-by":"publisher","award":["358\/2021"],"award-info":[{"award-number":["358\/2021"]}],"id":[{"id":"10.13039\/501100009983","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Non-ischaemic cardiomyopathy (NICMP), an incurable disease terminating in systolic heart failure (heart failure with reduced ejection fraction [HFrEF]), causes immune activation, however anti-inflammatory treatment strategies so far have failed to alter the course of this disease. Myeloperoxidase (MPO), the principal enzyme in neutrophils, has cytotoxic, pro-fibrotic and nitric oxide oxidizing effects. Whether MPO inhibition ameliorates the phenotype in NICMP remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Prognostic information from MPO was derived from proteomic data of a large human cardiovascular health cohort (n\u2009=\u20093289). In a murine model of NICMP, we studied the mechanisms of MPO in this disease. In a case series, the MPO inhibitor was also evaluated in NICMP patients. Individuals with increased MPO revealed higher long-term mortality and worsening of heart failure, with impaired prognosis when MPO increased during follow-up. MPO infusion attenuated left ventricular ejection fraction (LVEF) in mice with NICMP, whereas genetic ablation or inhibition of MPO decreased systemic vascular resistance (SVR, 9.4\u2009\u00b1\u20090.7\u2009mmHg*min\/ml in NICMP vs. 6.7\u2009\u00b1\u20090.8\u2009mmHg*min\/ml in NICMP\/Mpo\u2212\/\u2212mice, n\u2009=\u20098, p\u2009=\u20090.006, data expressed as mean\u2009\u00b1\u2009standard error of the mean) and improved left ventricular function (LVEF 30.3\u2009\u00b1\u20092.2% in NICMP vs. 40.7\u2009\u00b1\u20091.1% in NICMP\/Mpo\u2212\/\u2212 mice, n\u2009=\u200916, p\u2009&amp;lt;\u20090.0001). Four patients diagnosed with NICMP and treated with an MPO inhibitor over 12\u2009weeks showed increase in LVEF, decline in natriuretic peptides and improved 6-min walking distance. MPO inhibitor-related changes in the proteome of NICMP patients predicted reduced mortality when related to the changes in the proteome of the above referenced cardiovascular health cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Myeloperoxidase predicts long-term outcome in HFrEF and its inhibition elicits systemic anti-inflammatory and vasodilating effects which translate into improved left ventricular function. MPO inhibition deserves further evaluation as a novel, complementary treatment strategy for HFrEF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ejhf.3435","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T07:10:27Z","timestamp":1725001827000},"page":"2269-2281","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of Myeloperoxidase to Treat Left Ventricular Dysfunction in Non-Ischaemic Cardiomyopathy"],"prefix":"10.1093","volume":"26","author":[{"given":"Simon","family":"Geissen","sequence":"first","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Braumann","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Adler","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, 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), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Mehrkens","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hof","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), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Guthoff","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), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"von Stein","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Witkowski","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University , D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Gerdes","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University , D\u00fcsseldorf 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,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Isermann","sequence":"additional","affiliation":[{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD) and Institute for Mitochondrial Diseases and Ageing, Medical Faculty, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Trifunovic","sequence":"additional","affiliation":[{"name":"Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD) and Institute for Mitochondrial Diseases and Ageing, Medical Faculty, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander C.","family":"Bunck","sequence":"additional","affiliation":[{"name":"Department of Radiology, Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Mollenhauer","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Winkels","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Adam","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Klinke","sequence":"additional","affiliation":[{"name":"Agnes Wittenborg Institute for Translational Cardiovascular Research, Clinic for General and Interventional Cardiology\/Angiology, Herz- und Diabeteszentrum NRW, University Hospital of the Ruhr-Universit\u00e4t Bochum , Bad Oeynhausen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor","family":"Buch","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"ten Cate","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hellmich","sequence":"additional","affiliation":[{"name":"Institute of Medical Statistics and Computational Biology (IMSB), Faculty of Medicine and University Hospital Cologne, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, Heinrich-Heine University , D\u00fcsseldorf ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Rudolph","sequence":"additional","affiliation":[{"name":"Agnes Wittenborg Institute for Translational Cardiovascular Research, Clinic for General and Interventional Cardiology\/Angiology, Herz- und Diabeteszentrum NRW, University Hospital of the Ruhr-Universit\u00e4t Bochum , Bad Oeynhausen ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp S.","family":"Wild","sequence":"additional","affiliation":[{"name":"Preventive Cardiology and Preventive Medicine, Department of Cardiology, University Medical Center of the Johannes Gutenberg-University Mainz , Mainz ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Rosenkranz","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Baldus","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and University Hospital Cologne, Clinic III for Internal Medicine, University of Cologne , Cologne ,","place":["Germany"]},{"name":"Cologne Cardiovascular Research Center (CCRC), University of Cologne , Cologne ,","place":["Germany"]},{"name":"Center for Molecular Medicine Cologne (CMMC), Faculty of Medicine and Faculty of Mathematics and Natural Sciences, University of Cologne , Cologne ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"2026010913035337500_ejhf3435-bib-0001","doi-asserted-by":"crossref","first-page":"1770","DOI":"10.1093\/eurheartj\/ehy005","article-title":"Mortality associated with heart failure with preserved vs. reduced ejection fraction in a prospective international 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