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Third-party-funded project

Title:
Morphogenesis of the cardiac valves focussing on congenital heart disease with malformations involving more than one valve (polyvalvular disease).

Project management at the University of Würzburg:

• Dr. med. Ulrike Bartram

Participating scientists:

• Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Niederlande:
• Prof. Dr. Adriana C. Gittenberger-de Groot
• Dr. Margot M. Bartelings
• Dr. Bianca Hogers
• Daniel D.G. M. Molin
• Dr. Petra Oosthoek
• Prof. Dr. Robert Poelmann
• Department of Pediatrics, University of Arizona College of Medicine, Tuscon, Arizona, USA:
• Dr. Ian N. Jongewaard
• Prof. Dr. Scott E. Klewer
• Department of Cell Biology, Neurobiology and Anatomy, University of Cinncinnati, Cinncinnati, Ohio, USA:
• Prof. Dr. Thomas Doetschman
• Dr. Azhar Mohamad

Abstract:
Malformations of the cardiac valves are frequent in congenital heart disease. While the pathomorphology of these anomalies in general is rather well defined, knowledge about normal valvular morphogenesis and the processes resulting in malformations is scarce. Based on the normal development of the cardiac valves and their differentiation from the endocardial cushions which function as primitive valves already, this project focused on the pathogenesis of malformations involving more than one cardiac valve since abnormal development of the endocardial cushions as the pathomorphogenetic basis of these anomalies is most evident in these anomalies.
The growth and differentiation factor TGFß (transforming growth factor) is of particular importance in cardiac morphogenesis. Therefore, the goal of this study was to analyze the role of the isoforms of TGFß in normal embryonic heart development and characterize the type of disturbances of endocardial cushion development caused by disruption of the TGFß2 gene in the mouse model.
In addition, the influence of the expression of extracellular matrix molecules ? such as collagens ? was studied.

Key words:
    cardiac morphogenesis
    congenital heart disease
    polyvalvular disease
    TGFß
    collagen VI

Projekt period: from 01.1999 to 12.2001

Funding institution:
DFG ( Sachmittelbeihilfe ) ,Granting date: 24.04.1999

Publications:

• Bartram U, Bartelings MM, Kramer HH, Gittenberger-de Groot AC. (2001). Congenital polyvalvular disease ? a review. Pediatr Cardiol. (monograph)
• Bartram U, Molin DGM, Wisse LJ, Mohamad A, Sanford LP, Doetschman T, Speer CP, Poelmann RE, Gittenberger-de Groot AC. (2001). Double-outlet right ventricle and overriding tricuspid valve reflect disturbances of myocardialization, endocardial cushion differentiation, and apoptosis in TGFß2 knockout mice. Circulation. (monograph)
• Gittenberger-de Groot AC, Bartram U, Oosthoek PW, Bartelings MM, Hogers B, Jongewaard IN, Klewer SE. (2002). Increased cardiac type VI collagen expression in fetuses with trisomy 21. Anat Rec. (monograph)
• Bartram U, Molin DGM, van der Heiden K, van Iperen L, Speer CP, Gittenberger-de Groot AC. (zur Veröffentlichung eingereicht). Expression of TgFß1-3 mRNA during cardiac morphogenesis. Dev Dyn. (monograph)