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.
[1]Chinese Acad Sci, Grad Sch, Shanghai Inst Biol Sci, Key Lab Nutr & Metab,Inst Nutr Sci, Shanghai 200031, Peoples R China.
[2]Nanjing Univ, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China.
[3]Shanghai Jiao Tong Univ, Shanghai Childrens Med Ctr, Sch Med, Shanghai 200092, Peoples R China.
[4]Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[5]Inst Biotechnol, State Key Lab Prote, Beijing 100071, Peoples R China.
[6]Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China.
[7]Univ Naples Federico II, Inst Genet & Biophys CNR, I-80138 Naples, Italy.
[8]Tongji Univ, Sch Med, Shanghai 201000, Peoples R China.
[9]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Shanghai 200072, Peoples R China.
[10]Univ Houston, Dept Biol & Biochem, Houston, TX 77204 USA.
[11]Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[12]Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RC Leiden, Netherlands.
[13]Stanford Univ, Sch Med, Dept Biol, Stanford, CA 94305 USA.
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