Coronary arteries form by developmental reprogramming of venous cells

Kristy Red-Horse, Hiroo Ueno, Irving L. Weissman and Mark A. Krasnow ()
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Kristy Red-Horse: Department of Biochemistry and Howard Hughes Medical Institute,
Hiroo Ueno: Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305-5307, USA
Irving L. Weissman: Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305-5307, USA
Mark A. Krasnow: Department of Biochemistry and Howard Hughes Medical Institute,

Nature, 2010, vol. 464, issue 7288, 549-553

Abstract: Abstract Coronary artery disease is the leading cause of death worldwide. Determining the coronary artery developmental program could aid understanding of the disease and lead to new treatments, but many aspects of the process, including their developmental origin, remain obscure. Here we show, using histological and clonal analysis in mice and cardiac organ culture, that coronary vessels arise from angiogenic sprouts of the sinus venosus—the vein that returns blood to the embryonic heart. Sprouting venous endothelial cells dedifferentiate as they migrate over and invade the myocardium. Invading cells differentiate into arteries and capillaries; cells on the surface redifferentiate into veins. These results show that some differentiated venous cells retain developmental plasticity, and indicate that position-specific cardiac signals trigger their dedifferentiation and conversion into coronary arteries, capillaries and veins. Understanding this new reprogramming process and identifying the endogenous signals should suggest more natural ways of engineering coronary bypass grafts and revascularizing the heart.

Date: 2010
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DOI: 10.1038/nature08873

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