Macrophage-Expressed Coagulation Factor 7 Promotes Adverse Cardiac Remodeling.

fibrosis heart failure homeostasis macrophages myocardial infarction

Journal

Circulation research
ISSN: 1524-4571
Titre abrégé: Circ Res
Pays: United States
ID NLM: 0047103

Informations de publication

Date de publication:
05 Sep 2024
Historique:
medline: 5 9 2024
pubmed: 5 9 2024
entrez: 5 9 2024
Statut: aheadofprint

Résumé

Excess fibrotic remodeling causes cardiac dysfunction in ischemic heart disease, driven by MAP (mitogen-activated protein) kinase-dependent TGF-ß1 (transforming growth factor-ß1) activation by coagulation signaling of myeloid cells. How coagulation-inflammatory circuits can be specifically targeted to achieve beneficial macrophage reprogramming after myocardial infarction (MI) is not completely understood. Mice with permanent ligation of the left anterior descending artery were used to model nonreperfused MI and analyzed by single-cell RNA sequencing, protein expression changes, confocal microscopy, and longitudinal monitoring of recovery. We probed the role of the tissue factor (TF)-factor 7 (F7)-integrin ß1-PAR2 (protease-activated receptor 2) signaling complex by utilizing genetic mouse models and pharmacological intervention. Cleavage-insensitive PAR2 Extravascular TF-F7-PAR2 complex signaling drives inflammatory macrophage polarization in ischemic heart disease. Targeting this signaling complex for specific therapeutic macrophage reprogramming following MI attenuates cardiac fibrosis and improves cardiovascular function.

Sections du résumé

BACKGROUND UNASSIGNED
Excess fibrotic remodeling causes cardiac dysfunction in ischemic heart disease, driven by MAP (mitogen-activated protein) kinase-dependent TGF-ß1 (transforming growth factor-ß1) activation by coagulation signaling of myeloid cells. How coagulation-inflammatory circuits can be specifically targeted to achieve beneficial macrophage reprogramming after myocardial infarction (MI) is not completely understood.
METHODS UNASSIGNED
Mice with permanent ligation of the left anterior descending artery were used to model nonreperfused MI and analyzed by single-cell RNA sequencing, protein expression changes, confocal microscopy, and longitudinal monitoring of recovery. We probed the role of the tissue factor (TF)-factor 7 (F7)-integrin ß1-PAR2 (protease-activated receptor 2) signaling complex by utilizing genetic mouse models and pharmacological intervention.
RESULTS UNASSIGNED
Cleavage-insensitive PAR2
CONCLUSIONS UNASSIGNED
Extravascular TF-F7-PAR2 complex signaling drives inflammatory macrophage polarization in ischemic heart disease. Targeting this signaling complex for specific therapeutic macrophage reprogramming following MI attenuates cardiac fibrosis and improves cardiovascular function.

Identifiants

DOI: 10.1161/CIRCRESAHA.123.324114 PMID: 39234697
pubmed: 39234697
doi: 10.1161/CIRCRESAHA.123.324114
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Auteurs

Venkata Garlapati (V)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).
Department of Cardiology, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., S.F., W.R., P.W.).
German Center for Cardiovascular Research-Partner site Rhine-Main, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., W.R., P.W.).

Qi Luo (Q)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).
Department of Cardiology, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., S.F., W.R., P.W.).
German Center for Cardiovascular Research-Partner site Rhine-Main, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., W.R., P.W.).
Department of Biochemistry, CARIM School for Cardiovascular Research Maastricht University, the Netherlands (Q.L.).

Jens Posma (J)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).

Melania Aluia (M)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).
Department of Cardiology, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., S.F., W.R., P.W.).
German Center for Cardiovascular Research-Partner site Rhine-Main, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., W.R., P.W.).
ORCID: 0009-0007-6801-8783

Than Son Nguyen (TS)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).

Kristin Grunz (K)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).

Michael Molitor (M)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).
Department of Cardiology, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., S.F., W.R., P.W.).
German Center for Cardiovascular Research-Partner site Rhine-Main, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., W.R., P.W.).
ORCID: 0000-0001-6075-4996

Stefanie Finger (S)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).
Department of Cardiology, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., S.F., W.R., P.W.).

Gregory Harms (G)

Institute of Immunology and Research Center for Immunotherapy, University Medical Center Mainz, Germany. (G.H., T.B.).
and Cell Biology Unit, University Medical Center Mainz, Germany. (G.H.).
Department of Biology, Wilkes University, Wilkes-Barre, PA (G.H.).
ORCID: 0000-0001-7167-7738

Tobias Bopp (T)

Institute of Immunology and Research Center for Immunotherapy, University Medical Center Mainz, Germany. (G.H., T.B.).
ORCID: 0000-0002-3232-8065

Wolfram Ruf (W)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).
Department of Cardiology, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., S.F., W.R., P.W.).
German Center for Cardiovascular Research-Partner site Rhine-Main, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., W.R., P.W.).
Department of Immunology and Microbiology, Scripps Research, La Jolla, CA (W.R.).
ORCID: 0000-0002-6064-2166

Philip Wenzel (P)

Center for Thrombosis and Hemostasis, University Medical Center Mainz, Germany. (V.G., Q.L., J.P., M.A., T.S.N., K.G., M.M., S.F., W.R., P.W.).
Department of Cardiology, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., S.F., W.R., P.W.).
German Center for Cardiovascular Research-Partner site Rhine-Main, University Medical Center Mainz, Germany. (V.G., Q.L., M.A., M.M., W.R., P.W.).
ORCID: 0000-0002-5397-2781

Classifications MeSH