Genetic Fate Mapping Defines the Vascular Potential of Endocardial Cells in the Adult Heart
Rationale: Endocardium is the major source of coronary endothelial cells 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.
Objective: To define the vascular potential of adult endocardium in homeostasis and after cardiac injuries by fate mapping studies.
Methods and Results: We generate an inducible adult endocardial Cre line (Npr3-CreER) and show that Npr3-CreER 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 endothelial cells during cardiac homeostasis. To examine the formation of blood vessels from endocardium after injury, we generate four cardiac injury models with Npr3-CreER mice: myocardial infarction (MI), myocardial ischemia-reperfusion (IR), cryoinjury (CI), transverse aortic constriction (TAC). Lineage tracing experiments show that adult endocardium minimally contributes to coronary endothelial cells after MI. In the IR, CI or TAC models, adult endocardial cells do not give rise to any vascular endothelial cells, and they remain on the inner surface of myocardium that connects with lumen circulation. In the MI 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 re-located and trapped in the infarcted myocardium by transplantation or myocardial constriction model, very few endocardial cells survive and gain vascular endothelial cell properties, and their contribution to neovascularization in the injured myocardium remains minimal.
Conclusions: Unlike its fetal or neonatal counterpart, adult endocardium naturally generates minimal, if any, coronary arteries or vascular endothelial cells during cardiac homeostasis or after injuries.
- Received November 7, 2017.
- Revision received January 22, 2018.
- Accepted January 25, 2018.