From the State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology (J.T., H.Z., L.H., X.H., Y.L., W.P., W.Y., L.Z., B.Z.) and Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences (J.T., H.Z., L.H., X.H., Y.L., W.P., W.Y., L.Z., B.Z.), Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, China; School of Life Science and Technology, ShanghaiTech University, China (H.Z., B.Z.); Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Jinan University, Guangzhou, China (D.C., B.Z.); and Department of Chemical Pathology, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, SAR, China (K.O.L.).
Circ Res. 2018 Mar 30;122(7):984-993. doi: 10.1161/CIRCRESAHA.117.312354. Epub 2018 Jan 26.
Endocardium is the major source of coronary endothelial cells (ECs) in the fetal and neonatal hearts. It remains unclear whether endocardium in the adult stage is also the main origin of neovascularization after cardiac injury.
To define the vascular potential of adult endocardium in homeostasis and after cardiac injuries by fate-mapping studies.
We generate an inducible adult endocardial Cre line ( [natriuretic peptide receptor C]-) and show that efficiently and specifically labels endocardial cells but not coronary blood vessels in the adult heart. The adult endocardial cells do not contribute to any vascular ECs during cardiac homeostasis. To examine the formation of blood vessels from endocardium after injury, we generate 4 cardiac injury models with mice: myocardial infarction, myocardial ischemia-reperfusion, cryoinjury, and transverse aortic constriction. Lineage tracing experiments show that adult endocardium minimally contributes to coronary ECs after myocardial infarction. In the myocardial ischemia-reperfusion, cryoinjury, or transverse aortic constriction models, adult endocardial cells do not give rise to any vascular ECs, and they remain on the inner surface of myocardium that connects with lumen circulation. In the myocardial infarction model, very few endocardial cells are trapped in the infarct zone of myocardium shortly after ligation of coronary artery, indicating the involvement of endocardial entrapment during blood vessels formation. When these adult endocardial cells are relocated and trapped in the infarcted myocardium by transplantation or myocardial constriction model, very few endocardial cells survive and gain vascular EC properties, and their contribution to neovascularization in the injured myocardium remains minimal.
Unlike its fetal or neonatal counterpart, adult endocardium naturally generates minimal, if any, coronary arteries or vascular ECs during cardiac homeostasis or after injuries.
心内膜是胎儿和新生儿心脏中冠状动脉内皮细胞（ECs）的主要来源。目前尚不清楚成年阶段的心内膜是否也是心脏损伤后新生血管形成的主要来源。
通过谱系追踪研究确定成年心内膜在心脏稳态和心脏损伤后的血管潜能。
我们构建了一个可诱导的成年心内膜 Cre 线（[利钠肽受体 C]-），并证实其能有效地、特异性地标记成年心脏中的心内膜细胞，但不标记冠状动脉血管。成年心内膜细胞在心脏稳态时不会分化为任何血管内皮细胞。为了研究损伤后心内膜形成血管的情况，我们利用 小鼠构建了 4 种心脏损伤模型：心肌梗死、心肌缺血再灌注、冷冻损伤和主动脉缩窄。谱系追踪实验表明，成年心内膜在心梗后仅少量分化为冠状动脉 ECs。在心肌缺血再灌注、冷冻损伤或主动脉缩窄模型中，成年心内膜细胞不会分化为任何血管内皮细胞，它们仍位于与腔循环相连的心肌内膜表面。在心肌梗死模型中，冠状动脉结扎后不久，只有极少数心内膜细胞被捕获在心梗区，提示在血管形成过程中心内膜捕获的参与。当这些成年心内膜细胞通过移植或心肌缩窄模型重新定位并捕获在梗死的心肌中时，只有极少数心内膜细胞存活并获得血管内皮细胞特性，它们对损伤心肌中的新生血管形成的贡献仍然很小。
与胎儿或新生儿的心内膜不同，成年心内膜在心脏稳态或损伤后，天然产生的冠状动脉或血管内皮细胞很少（如果有的话）。
