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Updated: May 10, 2026

Analysis of Coronary Vessels in Cleared Embryonic Hearts
Published on: December 7, 2016
Subepicardial endothelial cells invade the embryonic ventricle wall to form coronary arteries
Xueying Tian1, Tianyuan Hu, Hui Zhang
1Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Insights
Subepicardial endothelial cells are the primary source of coronary arteries and veins in the developing heart. These cells originate from the sinus venosus and atrium endocardium, forming both vessel types.
Area of Science:
- Cardiovascular Biology
- Developmental Biology
- Vascular Biology
Background:
- Coronary arteries supply blood to the heart muscle, and understanding their development is crucial for treating coronary artery diseases.
- The precise origins of coronary vessels, including contributions from the proepicardium, sinus venosus (SV), and endocardium, remain an active area of research.
Purpose of the Study:
- To investigate the developmental origins of coronary arteries and veins using a novel genetic tool.
- To identify the major cellular sources contributing to the formation of intramyocardial coronary vessels.
Main Methods:
- Development and utilization of a new AplnCreER mouse line for inducible genetic fate tracing of coronary vessel development.
- Quantitative analysis of coronary development and timed induction of fate tracing in the AplnCreER mouse model.
- In vitro explant assays to determine the origin of subepicardial endothelial cells.
Main Results:
- Subepicardial endothelial cells (ECs) were identified as the predominant source of intramyocardial coronary vessels, forming both arteries and veins.
- Fate mapping revealed that these subepicardial ECs originate mainly from the endocardium of the sinus venosus and atrium, excluding ventricular endocardium.
- Clonal analysis demonstrated that individual subepicardial ECs contribute equally to the development of both coronary arteries and veins.
Conclusions:
- Subepicardial endothelial cells are the primary progenitors of the ventricular wall's intramyocardial coronary arteries.
- Coronary arteries and veins share a common developmental origin from subepicardial endothelial cells derived from the sinus venosus and atrial endocardium.
Abstract:
Coronary arteries bring blood flow to the heart muscle. Understanding the developmental program of the coronary arteries provides insights into the treatment of coronary artery diseases. Multiple sources have been described as contributing to coronary arteries including the proepicardium, sinus venosus (SV), and endocardium. However, the developmental origins of coronary vessels are still under intense study. We have produced a new genetic tool for studying coronary development, an AplnCreER mouse line, which expresses an inducible Cre recombinase specifically in developing coronary vessels. Quantitative analysis of coronary development and timed induction of AplnCreER fate tracing showed that the progenies of subepicardial endothelial cells (ECs) both invade the compact myocardium to form coronary arteries and remain on the surface to produce veins. We found that these subepicardial ECs are the major sources of intramyocardial coronary vessels in the developing heart. In vitro explant assays indicate that the majority of these subepicardial ECs arise from endocardium of the SV and atrium, but not from ventricular endocardium. Clonal analysis of Apln-positive cells indicates that a single subepicardial EC contributes equally to both coronary arteries and veins. Collectively, these data suggested that subepicardial ECs are the major source of intramyocardial coronary arteries in the ventricle wall, and that coronary arteries and veins have a common origin in the developing heart.
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