Browsing by Author "van den Heuvel, Joop"

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    Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase
    (American Association for the Advancement of Science, 2022) Reboll, Marc R.; Klede, Stefanie; Taft, Manuel H.; Cai, Chen-Leng; Field, Loren J.; Lavine, Kory J.; Koenig, Andrew L.; Fleischauer, Jenni; Meyer, Johann; Schambach, Axel; Niessen, Hans W.; Kosanke, Maike; van den Heuvel, Joop; Pich, Andreas; Bauersachs, Johann; Wu, Xuekun; Zheng, Linqun; Wang, Yong; Korf-Klingebiel, Mortimer; Polten, Felix; Wollert, Kai C.; Pediatrics, School of Medicine
    Effective tissue repair after myocardial infarction entails a vigorous angiogenic response, guided by incompletely defined immune cell-endothelial cell interactions. We identify the monocyte- and macrophage-derived cytokine METRNL (meteorin-like) as a driver of postinfarction angiogenesis and high-affinity ligand for the stem cell factor receptor KIT (KIT receptor tyrosine kinase). METRNL mediated angiogenic effects in cultured human endothelial cells through KIT-dependent signaling pathways. In a mouse model of myocardial infarction, METRNL promoted infarct repair by selectively expanding the KIT-expressing endothelial cell population in the infarct border zone. Metrnl-deficient mice failed to mount this KIT-dependent angiogenic response and developed severe postinfarction heart failure. Our data establish METRNL as a KIT receptor ligand in the context of ischemic tissue repair.