TY - JOUR
T1 - Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling
AU - Wu, Bingruo
AU - Zhang, Zheng
AU - Lui, Wendy
AU - Chen, Xiangjian
AU - Wang, Yidong
AU - Chamberlain, Alyssa A.
AU - Moreno-Rodriguez, Ricardo A.
AU - Markwald, Roger R.
AU - O'Rourke, Brian P.
AU - Sharp, David J.
AU - Zheng, Deyou
AU - Lenz, Jack
AU - Baldwin, H. Scott
AU - Chang, Ching Pin
AU - Zhou, Bin
N1 - Funding Information:
We are grateful to Napoleone Ferrara, Janet Rossant, Kyunghee Choi, and Gordon Fishell for Vegf-a f/f , Vegfr-2 f/f , RCE fsEGFP mice. We thank Drs. Bernice Morrow and Richard Kitsis for critical reading of the manuscript and Tatyana Harris for the illustration. B.Z. was supported by NIH (HL078881), AHA (0435128N) and Tuner-Hazinski Research Award. H.S.B. and C.-P.C. were supported by NIH (HL100398 and HL85345, respectively).
PY - 2012/11/21
Y1 - 2012/11/21
N2 - The origins and developmental mechanisms of coronary arteries are incompletely understood. We show here by fate mapping, clonal analysis, and immunohistochemistry that endocardial cells generate the endothelium of coronary arteries. Dye tracking, live imaging, and tissue transplantation also revealed that ventricular endocardial cells are not terminally differentiated; instead, they are angiogenic and form coronary endothelial networks. Myocardial Vegf-a or endocardial Vegfr-2 deletion inhibited coronary angiogenesis and arterial formation by ventricular endocardial cells. In contrast, lineage and knockout studies showed that endocardial cells make a small contribution to the coronary veins, the formation of which is independent of myocardial-to-endocardial Vegf signaling. Thus, contrary to the current view of a common source for the coronary vessels, our findings indicate that the coronary arteries and veins have distinct origins and are formed by different mechanisms. This information may help develop better cell therapies for coronary artery disease.
AB - The origins and developmental mechanisms of coronary arteries are incompletely understood. We show here by fate mapping, clonal analysis, and immunohistochemistry that endocardial cells generate the endothelium of coronary arteries. Dye tracking, live imaging, and tissue transplantation also revealed that ventricular endocardial cells are not terminally differentiated; instead, they are angiogenic and form coronary endothelial networks. Myocardial Vegf-a or endocardial Vegfr-2 deletion inhibited coronary angiogenesis and arterial formation by ventricular endocardial cells. In contrast, lineage and knockout studies showed that endocardial cells make a small contribution to the coronary veins, the formation of which is independent of myocardial-to-endocardial Vegf signaling. Thus, contrary to the current view of a common source for the coronary vessels, our findings indicate that the coronary arteries and veins have distinct origins and are formed by different mechanisms. This information may help develop better cell therapies for coronary artery disease.
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U2 - 10.1016/j.cell.2012.10.023
DO - 10.1016/j.cell.2012.10.023
M3 - Article
C2 - 23178125
AN - SCOPUS:84870043996
SN - 0092-8674
VL - 151
SP - 1083
EP - 1096
JO - Cell
JF - Cell
IS - 5
ER -