Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase

• DOI: 10.1126/science.abn3027
• Publication Date: 2022-06-16T17:56:37Z
• Authors: Marc R. Reboll; Stefanie Klede; Manuel H. Taft; Chen-Leng Cai; Loren J. Field; Kory J. Lavine; Andrew L. Koenig; Jenni Fleischauer; Johann Meyer; Axel Schambach; Hans W. Niessen; Maike Kosanke; Joop van den Heuvel; Andreas Pich; Johann Bauersachs; Xuekun Wu; Linqun Zheng; Yong Wang; Mortimer Korf-Kli...; Felix Polten; Kai C. Wollert
• Keywords: Heart Failure; 0303 health sciences; Macrophages; Myocardial Infarction; Endothelial Cells; Neovascularization, Physiologic; Heart failure; Ligands; Mice, Mutant Strains; 3. Good health; Myocardial infarction; Mice; Proto-Oncogene Proteins c-kit; 03 medical and health sciences; Adipokines; Animals; Cytokines; Nerve growth factors; Nerve Growth Factors; Cells, Cultured

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 driver of postinfarction angiogenesis high-affinity ligand for stem factor receptor KIT (KIT tyrosine kinase). mediated effects in cultured human endothelial cells through KIT-dependent signaling pathways. In mouse model infarction, promoted infarct selectively expanding KIT-expressing population border zone. Metrnl -deficient mice failed to mount this response developed severe heart failure. Our data establish context ischemic repair.