Hardy, S., Liesinger, L., Patrick, R., Poettler, M., Rech, L., Gindlhuber, J., Mabotuwana, N., Ashour, D., Stangl, V., Bigland, M., Murtha, L., Starkey, M., Scherr, D., Hansbro, P. M., Hoefler, G., Ramos, G., Cochain, C., Harvey, R., Birner-Grünberger, R., … Rainer, P. P. (2023). Extracellular Matrix Protein-1 as a Mediator of Inflammation-Induced Fibrosis After Myocardial Infarction. JACC: Basic to Translational Science. https://doi.org/10.1016/j.jacbts.2023.05.010
Irreversible fibrosis is a hallmark of myocardial infarction (MI) and heart failure. Extracellular matrix protein-1 (ECM-1) is up-regulated in these hearts, localized to fibrotic, inflammatory, and perivascular areas. ECM-1 originates predominantly from fibroblasts, macrophages, and pericytes/vascular cells in uninjured human and mouse hearts, and from M1 and M2 macrophages and myofibroblasts after MI. ECM-1 stimulates fibroblast-to-myofibroblast transition, up-regulates key fibrotic and inflammatory pathways, and inhibits cardiac fibroblast migration. ECM-1 binds HuCFb cell surface receptor LRP1, and LRP1 inhibition blocks ECM-1 from stimulating fibroblast-to-myofibroblast transition, confirming a novel ECM-1-LRP1 fibrotic signaling axis. ECM-1 may represent a novel mechanism facilitating inflammation-fibrosis crosstalk.
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Project title:
Lipidhydrolyse im Krebs und in Lipid-assoziierten Krankheiten: F 7309-B21 (FWF Fonds zur Förderung der wissenschaftlichen Forschung (FWF))
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Project (external):
Austrian Science Fund (FWF) Austrian Science Fund (FWF) Austrian Science Fund (FWF) John Hunter Charitable Trust Hunter Medical Research Institute and Emlyn and Jennie Thomas Postgraduate Medical Research Scholarship Hunter Medical Research Institute and Emlyn and Jennie Thomas Postgraduate Medical Research Scholarship National Health and Medical Research Council (NHMRC) National Health and Medical Research Council (NHMRC) National Health and Medical Research Council (NHMRC) National Health and Medical Research Council (NHMRC) National Health and Medical Research Council (NHMRC) National Health and Medical Research Council (NHMRC) NHMRC Senior Principal Research Fellowship Stem Cells Australia Australian Research Council Foundation Leducq Foundation Leducq Interdisciplinary Centre for Clinical Research, University Hospital Würzburg Interdisciplinary Centre for Clinical Research, University Hospital Würzburg German Research Foundation German Research Foundation German Research Foundation German Research Foundation European Research Area Network—Cardiovascular Diseases/German Federal Ministry of Education and Research
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Project ID:
W 1226 K LI645 I 4168-B G1800510 G2100164 G1800696 2000615 1074386 1079187 1175134 1156898 20000483 1118576 SR110001002 DE170100226 15CVD03 13CVD01 E-353 E-354 471705758 458539578 453989101 411619907 01KL1902
CC BY-NC-ND 4.0
