Cell-specific activation of Wnt signaling in healing after myocardial infarction
Funding period: 2021-2025

Project Leaders
Abstract
Myocardial injury elicits a sterile immune response that impacts healing and subsequent ventricular function. We have recently identified a novel role for Wnt signaling in local activation of monocytes. In this subproject, we will determine the role of the Wnt signaling regulator FAM129B and the non-canonical Wnt signaling receptor ROR2, and their involvement in immune cell activation following myocardial infarction. It furthermore aims to elucidate the cell-type specific secretion of Wnt proteins and Wnt modulators and the spatio-temporal activation of Wnt signaling in cardiac cells that participate in the healing process after myocardial injury.

Project-related Publications
Blockade of Wnt Secretion Attenuates Myocardial Ischemia-Reperfusion Injury by Modulating the Inflammatory Response
A Minimal-Invasive Approach for Standardized Induction of Myocardial Infarction in Mice
Circ Res. 2020 Oct 9;127(9):1214-1216. doi: 10.1161/CIRCRESAHA.120.317794. Epub 2020 Aug 28. PMID: 32854590
Learn moreSecretome Analysis of Cardiomyocytes Identifies PCSK6 (Proprotein Convertase Subtilisin/Kexin Type 6) as a Novel Player in Cardiac Remodeling After Myocardial Infarction
Novel functions of macrophages in the heart: insights into electrical conduction, stress, and diastolic dysfunction
Eur Heart J. 2020 Mar 1;41(9):989-994. doi: 10.1093/eurheartj/ehz159. PMID: 30945736
Learn moreThe role of Wnt signaling in the healing myocardium: a focus on cell specificity
Basic Res Cardiol. 2018 Oct 16;113(6):44. doi: 10.1007/s00395-018-0705-y. PMID: 30327885
Learn moreSilencing the CSF-1 Axis Using Nanoparticle Encapsulated siRNA Mitigates Viral and Autoimmune Myocarditis
Front Immunol. 2018 Oct 8;9:2303. doi: 10.3389/fimmu.2018.02303. eCollection 2018. PMID: 30349538
Learn moreThe cardiac microenvironment uses non-canonical WNT signaling to activate monocytes after myocardial infarction
EMBO Mol Med. 2017 Sep;9(9):1279-1293. doi: 10.15252/emmm.201707565. PMID: 28774883
Learn moreSilencing of CCR2 in myocarditis
Eur Heart J. 2015 Jun 14;36(23):1478-88. doi: 10.1093/eurheartj/ehu225. Epub 2014 Jun 20. PMID: 24950695
Learn moreRapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis
J Exp Med. 2012 Jan 16;209(1):123-37. doi: 10.1084/jem.20111009. Epub 2012 Jan 2. PMID: 22213805
Learn moreTherapeutic siRNA silencing in inflammatory monocytes in mice
Nat Biotechnol. 2011 Oct 9;29(11):1005-10. doi: 10.1038/nbt.1989. PMID: 21983520
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