TY - JOUR
T1 - Extracellular Matrix Protein-1 as a Mediator of Inflammation-Induced Fibrosis After Myocardial Infarction
AU - Hardy, Sean A.
AU - Liesinger, Laura
AU - Patrick, Ralph
AU - Poettler, Maria
AU - Rech, Lavinia
AU - Gindlhuber, Juergen
AU - Mabotuwana, Nishani S.
AU - Ashour, Diyaa Eldin
AU - Stangl, Verena
AU - Bigland, Mark
AU - Murtha, Lucy A.
AU - Starkey, Malcolm R.
AU - Scherr, Daniel
AU - Hansbro, Philip M.
AU - Hoefler, Gerald
AU - Campos Ramos, Gustavo
AU - Cochain, Clement
AU - Harvey, Richard P.
AU - Birner-Gruenberger, Ruth
AU - Boyle, Andrew J.
AU - Rainer, Peter P.
N1 - Funding Information:
The authors thank Viktoria Trummer-Herbst, Andreas Somma, and Sylvia Schauer, Medical University of Graz, Austria, for their expert technical assistance.
Publisher Copyright:
© 2023 The Authors
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - extracellular matrix
KW - fibroblasts
KW - fibrosis
KW - heart
KW - inflammation
KW - myocardial infarction
UR - http://www.scopus.com/inward/record.url?scp=85173661172&partnerID=8YFLogxK
U2 - 10.1016/j.jacbts.2023.05.010
DO - 10.1016/j.jacbts.2023.05.010
M3 - Article
C2 - 38205347
AN - SCOPUS:85173661172
SN - 2452-302X
VL - 8
SP - 1539
EP - 1554
JO - JACC: Basic to Translational Science
JF - JACC: Basic to Translational Science
IS - 12
ER -