Circulation Research. 2004;95:459-470
doi: 10.1161/01.RES.0000141146.95728.da
doi: 10.1161/01.RES.0000141146.95728.da
© 2004 American Heart Association, Inc.
Reviews |
Heart Valve Development
Endothelial Cell Signaling and Differentiation
From the Vascular Biology Program and Department of Surgery, Children’s Hospital Boston, Harvard Medical School, Boston, Mass.
Correspondence to Joyce Bischoff, PhD, Vascular Biology Program, Children’s Hospital Boston, 300 Longwood Ave, Boston, MA 02115. E-mail joyce.bischoff{at}childrens.harvard.edu
This Review is part of a thematic series on Vascular Cell Diversity, which includes the following articles:
Heart Valve Development: Endothelial Cell Signaling and Differentiation
Endothelial/Pericyte Interaction
Endothelial-ECM: Biosynthesis, Remodeling, and Functions
Smooth Muscle Cell Diversity
Joyce Bischoff Editor
During the past decade, single gene disruption in mice and large-scale mutagenesis screens in zebrafish have elucidated many fundamental genetic pathways that govern early heart patterning and differentiation. Specifically, a number of genes have been revealed serendipitously to play important and selective roles in cardiac valve development. These initially surprising results have now converged on a finite number of signaling pathways that regulate endothelial proliferation and differentiation in developing and postnatal heart valves. This review highlights the roles of the most well-established ligands and signaling pathways, including VEGF, NFATc1, Notch, Wnt/ß-catenin, BMP/TGF-ß, ErbB, and NF1/Ras. Based on the interactions among and relative timing of these pathways, a signaling network model for heart valve development is proposed.
Key Words: heart development • heart valves • valvular heart disease • NFAT • VEGF • TGF-ß
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