Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart

Nat Commun. 2014 Jul 29:5:4552. doi: 10.1038/ncomms5552.

Abstract

The origin and developmental mechanisms underlying coronary vessels are not fully elucidated. Here we show that myocardium-derived angiopoietin-1 (Ang1) is essential for coronary vein formation in the developing heart. Cardiomyocyte-specific Ang1 deletion results in defective formation of the subepicardial coronary veins, but had no significant effect on the formation of intramyocardial coronary arteries. The endothelial cells (ECs) of the sinus venosus (SV) are heterogeneous population, composed of APJ-positive and APJ-negative ECs. Among these, the APJ-negative ECs migrate from the SV into the atrial and ventricular myocardium in Ang1-dependent manner. In addition, Ang1 may positively regulate venous differentiation of the subepicardial APJ-negative ECs in the heart. Consistently, in vitro experiments show that Ang1 indeed promotes venous differentiation of the immature ECs. Collectively, our results indicate that myocardial Ang1 positively regulates coronary vein formation presumably by promoting the proliferation, migration and differentiation of immature ECs derived from the SV.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-1 / genetics
  • Angiopoietin-1 / metabolism*
  • Animals
  • Cell Differentiation / physiology
  • Chimera
  • Coronary Vessels / embryology*
  • DNA Primers / genetics
  • Embryonic Stem Cells / physiology*
  • Genetic Vectors / genetics
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Heart / embryology*
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Myocardium / metabolism*
  • Polymerase Chain Reaction
  • Real-Time Polymerase Chain Reaction

Substances

  • Angiopoietin-1
  • DNA Primers
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins