Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling

Bingruo Wu, Zheng Zhang, Wendy Lui, Xiangjian Chen, Yidong Wang, Alyssa A. Chamberlain, Ricardo A. Moreno-Rodriguez, Roger R. Markwald, Brian P. O'Rourke, David J. Sharp, Deyou Zheng, Jack Lenz, H. Scott Baldwin, Ching Pin Chang, Bin Zhou

Research output: Contribution to journalArticlepeer-review

202 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1083-1096
Number of pages14
JournalCell
Volume151
Issue number5
DOIs
StatePublished - Nov 21 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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