Reboll, Marc R.Klede, StefanieTaft, Manuel H.Cai, Chen-LengField, Loren J.Lavine, Kory J.Koenig, Andrew L.Fleischauer, JenniMeyer, JohannSchambach, AxelNiessen, Hans W.Kosanke, Maikevan den Heuvel, JoopPich, AndreasBauersachs, JohannWu, XuekunZheng, LinqunWang, YongKorf-Klingebiel, MortimerPolten, FelixWollert, Kai C.2024-01-172024-01-172022Reboll MR, Klede S, Taft MH, et al. Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase. Science. 2022;376(6599):1343-1347. doi:10.1126/science.abn3027https://hdl.handle.net/1805/38041Effective 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.en-USPublisher PolicyAdipokinesCytokinesHeart failureMacrophagesMyocardial infarctionNerve growth factorsArticle