1. Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase.
- Author
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Reboll, Marc R., Klede, Stefanie, Taft, Manuel H., Chen-Leng Cai, 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, Xuekun Wu, Linqun Zheng, Yong Wang, Korf-Klingebiel, Mortimer, and Polten, Felix
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MYOCARDIAL infarction , *CELL communication , *MACROPHAGES , *NEOVASCULARIZATION , *TYROSINE - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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