title: Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling.
abstract: 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.
authors.affiliation: Departments of Genetics, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Bingruo
authors.initials: B
authors.lastname: Wu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Wendy
authors.initials: W
authors.lastname: Lui
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Chen
authors.forename: Yidong
authors.initials: Y
authors.lastname: Wang
authors.forename: Alyssa A
authors.initials: AA
authors.lastname: Chamberlain
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Moreno-Rodriguez
authors.forename: Roger R
authors.initials: RR
authors.lastname: Markwald
authors.forename: Brian P
authors.initials: BP
authors.lastname: O'Rourke
authors.forename: David J
authors.initials: DJ
authors.lastname: Sharp
authors.forename: Deyou
authors.initials: D
authors.lastname: Zheng
authors.forename: Jack
authors.initials: J
authors.lastname: Lenz
authors.forename: H Scott
authors.initials: HS
authors.lastname: Baldwin
authors.forename: Ching-Pin
authors.initials: CP
authors.lastname: Chang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003331:Coronary Vessels / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D018919:Neovascularization, Physiologic; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2