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Coronary arteries form by developmental reprogramming of venous cells.

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.

Pubmed ID: 20336138


  • Red-Horse K
  • Ueno H
  • Weissman IL
  • Krasnow MA



Publication Data

March 25, 2010

Associated Grants

  • Agency: NICHD NIH HHS, Id: 2T32HD007249
  • Agency: NICHD NIH HHS, Id: T32 HD007249
  • Agency: NICHD NIH HHS, Id: T32 HD007249-20
  • Agency: NHLBI NIH HHS, Id: U01 HL099995
  • Agency: NHLBI NIH HHS, Id: U01 HL099999
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Biological Markers
  • Cell Differentiation
  • Cell Lineage
  • Coronary Vessels
  • Down-Regulation
  • Endothelial Cells
  • Gene Expression Regulation, Developmental
  • Gene Knock-In Techniques
  • Mice
  • Organ Culture Techniques