{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Garlapati V"],"funding":["BMBF","German Research Foundation","German Center for Cardiovascular Research","Else-Kröner-Fresenius-Foundation","Boehringer-Ingelheim-Foundation","Alexander-von-Humboldt Foundation"],"pagination":["e156436"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9927945"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["133(4)"],"pubmed_abstract":["Despite major advances in acute interventions for myocardial infarction (MI), adverse cardiac remodeling and excess fibrosis after MI causing ischemic heart failure (IHF) remain a leading cause of death worldwide. Here we identify a profibrotic coagulation signaling pathway that can be targeted for improved cardiac function following MI with persistent ischemia. Quantitative phosphoproteomics of cardiac tissue revealed an upregulated mitogen-activated protein kinase (MAPK) pathway in human IHF. Intervention in this pathway with trametinib improves myocardial function and prevents fibrotic remodeling in a murine model of non-reperfused MI. MAPK activation in MI requires myeloid cell signaling of protease-activated receptor 2 linked to the cytoplasmic domain of the coagulation initiator tiss"],"journal":["The Journal of clinical investigation"],"pubmed_title":["Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-β1-driven fibrotic remodeling in ischemic heart failure."],"pmcid":["PMC9927945"],"funding_grant_id":["N/A","AvH Ruf","01EO1003,01EO1503","371/47-1 FUGG,WE4361/7-1,KA-4035/1-1"],"pubmed_authors":["Munzel T","Ruf W","Harms GS","Knorr M","Vujacic-Mirski K","Wenzel P","Daiber A","Lagrange J","Gori T","Garlapati V","Finger S","Michna T","Brandt M","Tenzer S","Wild S","Karbach S","Efentakis P","Molitor M","Milting H","Wild J","Jung R"],"additional_accession":[]},"is_claimable":false,"name":"Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-β1-driven fibrotic remodeling in ischemic heart failure.","description":"Despite major advances in acute interventions for myocardial infarction (MI), adverse cardiac remodeling and excess fibrosis after MI causing ischemic heart failure (IHF) remain a leading cause of death worldwide. Here we identify a profibrotic coagulation signaling pathway that can be targeted for improved cardiac function following MI with persistent ischemia. Quantitative phosphoproteomics of cardiac tissue revealed an upregulated mitogen-activated protein kinase (MAPK) pathway in human IHF. Intervention in this pathway with trametinib improves myocardial function and prevents fibrotic remodeling in a murine model of non-reperfused MI. MAPK activation in MI requires myeloid cell signaling of protease-activated receptor 2 linked to the cytoplasmic domain of the coagulation initiator tiss","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-05-28T11:30:01.786Z","creation":"2025-02-19T03:26:38.138Z"},"accession":"S-EPMC9927945","cross_references":{"pubmed":["36548062"],"doi":["10.1172/JCI156436"]}}