A07

Cell-specific activation of Wnt signaling in healing after myocardial infarction

Funding period: 2021-2025

Project A07

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

A Minimal-Invasive Approach for Standardized Induction of Myocardial Infarction in Mice

Sicklinger F, Zhang Y, Lavine KJ, Simon N, Bucher V, Jugold M, Lehmann L, Konstandin MH, Katus HA, Leuschner F. Circ Res. 2020 Oct 9;127(9):1214-1216. doi: 10.1161/CIRCRESAHA.120.317794. Epub 2020 Aug 28. PMID: 32854590

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Secretome Analysis of Cardiomyocytes Identifies PCSK6 (Proprotein Convertase Subtilisin/Kexin Type 6) as a Novel Player in Cardiac Remodeling After Myocardial Infarction

Kuhn TC, Knobel J, Burkert-Rettenmaier S, Li X, Meyer IS, Jungmann A, Sicklinger F, Backs J, Lasitschka F, Müller OJ, Katus HA, Krijgsveld J*, Leuschner F*. Circulation. 2020 May 19;141(20):1628-1644. doi: 10.1161/CIRCULATIONAHA.119.044914. Epub 2020 Feb 26. *Joint senior authors.
PMID: 32100557

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Novel functions of macrophages in the heart: insights into electrical conduction, stress, and diastolic dysfunction

Leuschner F, Nahrendorf M. Eur Heart J. 2020 Mar 1;41(9):989-994. doi: 10.1093/eurheartj/ehz159. PMID: 30945736

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The role of Wnt signaling in the healing myocardium: a focus on cell specificity

Meyer IS, Leuschner F. Basic Res Cardiol. 2018 Oct 16;113(6):44. doi: 10.1007/s00395-018-0705-y. PMID: 30327885

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Silencing the CSF-1 Axis Using Nanoparticle Encapsulated siRNA Mitigates Viral and Autoimmune Myocarditis

Meyer IS, Goetzke CC, Kespohl M, Sauter M, Heuser A, Eckstein V, Vornlocher HP, Anderson DG, Haas J, Meder B, Katus HA, Klingel K, Beling A, Leuschner F. Front Immunol. 2018 Oct 8;9:2303. doi: 10.3389/fimmu.2018.02303. eCollection 2018. PMID: 30349538

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The cardiac microenvironment uses non-canonical WNT signaling to activate monocytes after myocardial infarction

Meyer IS, Jungmann A, Dieterich C, Zhang M, Lasitschka F, Werkmeister S, Haas J, Müller OJ, Boutros M, Nahrendorf M, Katus HA, Hardt SE, Leuschner F. EMBO Mol Med. 2017 Sep;9(9):1279-1293. doi: 10.15252/emmm.201707565. PMID: 28774883

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Silencing of CCR2 in myocarditis

Leuschner F, Courties G, Dutta P, Mortensen LJ, Gorbatov R, Sena B, Novobrantseva TI, Borodovsky A, Fitzgerald K, Koteliansky V, Iwamoto Y, Bohlender M, Meyer S, Lasitschka F, Meder B, Katus HA, Lin C, Libby P, Swirski FK, Anderson DG, Weissleder R, Nahrendorf M. Eur Heart J. 2015 Jun 14;36(23):1478-88. doi: 10.1093/eurheartj/ehu225. Epub 2014 Jun 20. PMID: 24950695

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Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis

Leuschner F, Rauch PJ, Ueno T, Gorbatov R, Marinelli B, Lee WW, Dutta P, Wei Y, Robbins C, Iwamoto Y, Sena B, Chudnovskiy A, Panizzi P, Keliher E, Higgins JM, Libby P, Moskowitz MA, Pittet MJ, Swirski FK, Weissleder R, Nahrendorf M. J Exp Med. 2012 Jan 16;209(1):123-37. doi: 10.1084/jem.20111009. Epub 2012 Jan 2. PMID: 22213805

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Therapeutic siRNA silencing in inflammatory monocytes in mice

Leuschner F, Dutta P, Gorbatov R, Novobrantseva TI, Donahoe JS, Courties G, Lee KM, Kim JI, Markmann JF, Marinelli B, Panizzi P, Lee WW, Iwamoto Y, Milstein S, Epstein-Barash H, Cantley W, Wong J, Cortez-Retamozo V, Newton A, Love K, Libby P, Pittet MJ, Swirski FK, Koteliansky V, Langer R, Weissleder R, Anderson DG, Nahrendorf M. Nat Biotechnol. 2011 Oct 9;29(11):1005-10. doi: 10.1038/nbt.1989. PMID: 21983520

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