Inhibition of Wnt signaling in monocytes and its possible role for healing in acute myocardial infarction.
Final Report Abstract
Immigration and activation of inflammatory cells in the heart contribute critically to healing and remodeling processes after myocardial infarction. We were previously able to show that Wnt signaling pathways are activated in the cardiac microenvironment and thus influence the phenotype of accumulating immune cells, especially monocytes. The funded project investigated how inhibiting the release of Wnt proteins affects the healing response after myocardial infarction in mice. Drug blockade of Wnt secretion led to a reduction in the accumulation of pro-inflammatory monocytes and resulted in an improved left ventricular function after experimental myocardial infarction. Following the hypothesis that cell-specific inhibition of the non-canonical signaling pathway in monocytes would lead to attenuated activation and subsequent dampened cardiac inflammation, blockade of the receptor ROR2 (a receptor crucial for non-canonical Wnt signaling) using nanoparticle-coated siRNA was tested. Unexpectedly, this approach resulted in increased inflammation in infarcted murine hearts and illustrates the necessity of further clarification of the possible therapeutic potential of Wnt signaling modification after myocardial infarction.
Publications
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The cardiac microenvironment uses non‐canonical WNT signaling to activate monocytes after myocardial infarction. EMBO Molecular Medicine, 9(9), 1279-1293.
Meyer, Ingmar Sören; Jungmann, Andreas; Dieterich, Christoph; Zhang, Min; Lasitschka, Felix; Werkmeister, Susann; Haas, Jan; Müller, Oliver J.; Boutros, Michael; Nahrendorf, Matthias; Katus, Hugo A.; Hardt, Stefan E. & Leuschner, Florian
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The role of Wnt signaling in the healing myocardium: a focus on cell specificity. Basic Research in Cardiology, 113(6).
Meyer, Ingmar Sören & Leuschner, Florian
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Novel functions of macrophages in the heart: insights into electrical conduction, stress, and diastolic dysfunction. European Heart Journal, 41(9), 989-994.
Leuschner, Florian & Nahrendorf, Matthias
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Blockade of Wnt Secretion Attenuates Myocardial Ischemia–Reperfusion Injury by Modulating the Inflammatory Response. International Journal of Molecular Sciences, 23(20), 12252.
Meyer, Ingmar Sören; Li, Xue; Meyer, Carina; Voloshanenko, Oksana; Pohl, Susann; Boutros, Michael; Katus, Hugo Albert; Frey, Norbert & Leuschner, Florian
