{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T22:58:48Z","timestamp":1784329128758,"version":"3.55.0"},"reference-count":86,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002808","name":"Carlsberg Foundation","doi-asserted-by":"publisher","award":["CF17-0209"],"award-info":[{"award-number":["CF17-0209"]}],"id":[{"id":"10.13039\/501100002808","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Foundation","doi-asserted-by":"publisher","award":["NNF20OC0059767"],"award-info":[{"award-number":["NNF20OC0059767"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003554","name":"Lundbeck Foundation","doi-asserted-by":"publisher","award":["R322-2019-2698"],"award-info":[{"award-number":["R322-2019-2698"]}],"id":[{"id":"10.13039\/501100003554","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation Programme Grant","doi-asserted-by":"publisher","award":["PG\/15\/16\/31330"],"award-info":[{"award-number":["PG\/15\/16\/31330"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Foundation Leducq","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>In patients with heart failure (HF), concomitant sinus node dysfunction (SND) is an important predictor of mortality, yet its molecular underpinnings are poorly understood. Using proteomics, this study aimed to dissect the protein and phosphorylation remodelling within the sinus node in an animal model of HF with concurrent SND.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>We acquired deep sinus node proteomes and phosphoproteomes in mice with heart failure and SND and report extensive remodelling. Intersecting the measured (phospho)proteome changes with human genomics pharmacovigilance data, highlighted downregulated proteins involved in electrical activity such as the pacemaker ion channel, Hcn4. We confirmed the importance of ion channel downregulation for sinus node physiology using computer modelling. Guided by the proteomics data, we hypothesized that an inflammatory response may drive the electrophysiological remodeling underlying SND in heart failure. In support of this, experimentally induced inflammation downregulated Hcn4 and slowed pacemaking in the isolated sinus node. From the proteomics data we identified proinflammatory cytokine-like protein galectin-3 as a potential target to mitigate the effect. Indeed, in vivo suppression of galectin-3 in the animal model of heart failure prevented SND.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Collectively, we outline the protein and phosphorylation remodeling of SND in heart failure, we highlight a role for inflammation in electrophysiological remodelling of the sinus node, and we present galectin-3 signalling as a target to ameliorate SND in heart failure.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvae054","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T11:55:21Z","timestamp":1714046121000},"page":"927-942","source":"Crossref","is-referenced-by-count":17,"title":["Proteomics couples electrical remodelling to inflammation in a murine model of heart failure with sinus node dysfunction"],"prefix":"10.1093","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-4894","authenticated-orcid":false,"given":"Konstantin","family":"Kahnert","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, 2200, Copenhagen N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Soattin","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, University of Manchester , Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert W","family":"Mills","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, 2200, Copenhagen N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Wilson","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, University of Manchester , Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT , UK"},{"name":"Institute of Systems, Molecular & Integrative Biology, University of Liverpool , Liverpool , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Maurya","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, 2200, Copenhagen N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Sorrentino","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, 2200, Copenhagen N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sami","family":"Al-Othman","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, University of Manchester , Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Tikhomirov","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, University of Manchester , Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT , UK"},{"name":"National Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine (ICTEM) , 72 Du Cane Road, London W12 0NN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yordi J","family":"van de Vegte","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Finn B","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, 2200, Copenhagen N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Achter","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Blegdamsvej 3B, 2200, Copenhagen N , Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Physics & Astronomy, Biological Physics Group, University of Manchester , Manchester , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Zi","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, University of Manchester , Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Sciences, University of Manchester , Core Technology Facility, 46 Grafton Street, Manchester, M13 9NT , UK"},{"name":"National Heart and Lung Institute, Imperial College London, Imperial Centre for Translational and Experimental Medicine (ICTEM) , 72 Du Cane Road, London W12 0NN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-686X","authenticated-orcid":false,"given":"Pim","family":"van der Harst","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Groningen, University Medical Center Groningen , Groningen , the Netherlands"},{"name":"Department of Cardiology, University Medical Center Utrecht , Utrecht , the 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