Meteorin-like promotes heart repair through endothelial KIT receptor tyrosine kinase.
Marc R RebollStefanie KledeManuel H TaftChen-Leng CaiLoren J FieldKory J LavineAndrew L KoenigJenni FleischauerJohann MeyerAxel SchambachHans W M NiessenMaike KosankeJoop van den HeuvelAndreas PichJohann BauersachsXuekun WuLinqun ZhengYong WangMortimer Korf-KlingebielFelix PoltenKai C WollertPublished in: Science (New York, N.Y.) (2022)
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.
Keyphrases
- endothelial cells
- tyrosine kinase
- heart failure
- high glucose
- epidermal growth factor receptor
- stem cells
- vascular endothelial growth factor
- atrial fibrillation
- physical activity
- adipose tissue
- acute myocardial infarction
- left ventricular
- electronic health record
- big data
- cell proliferation
- artificial intelligence
- bone marrow
- coronary artery disease
- epithelial mesenchymal transition
- machine learning
- acute coronary syndrome
- brain injury
- cerebral ischemia