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Novel biology of congenital heart defects

ESC Congress Report

  • Congenital heart disease present in 1% of live births
  • 40% of congenital heart disease affects outflow tract morphogenesis
  • Planar cell polarity of cardiac progenitor cells required for normal outflow tract development
  • Mutations of chromatin structure regulators may be another major contributor to congenital heart disease

This session, proposed by the Council on Basic Cardiovascular Science, focused on exciting new mechanistic insights into the etiology of congenital heart defects (CHD), that affect 1% of live births.
Regulators of chromatin structure, that control transcription factor accessibility during gene expression and have recently been identified in a de novo mutation screen to be a major contributor to CHD, were the subject of the first two talks.

Antonio Baldini (Naples) showed how components of the chromatin remodeling complex switch during early cardiac differentiation and how progenitor cell-specific subunits are essential for activity of the transcription factor TBX1, encoded by the major 22q11.2 deletion or DiGeorge syndrome gene. 22q11.2 deletion syndrome patients have a spectrum of CHD, including common outflow tract defects such as tetralogy of Fallot, and TBX1 also interacts with histone methyltransferase enzymes to modulate cis-regulatory sequence accessibility during cardiac differentiation.

Chromatin regulation is also a critical control step in gene expression changes during hypertrophy and heart failure as shown by the second speaker, Sarah Franklin (Salt Lake City). Here we learnt how changes in expression of histone methyl transferase genes modulate the hypertrophic response by repressing fetal gene re-expression.

The final talk of the session brought us back to the early heart, but away from chromatin, focusing on the addition of cardiac progenitor cells to the elongating heart tube. Here the planar cell polarity pathway, that orients cells within an epithelium, is essential for normal heart tube extension and great artery alignment with the ventricular chambers. Deborah Henderson (Newcastle) showed how planar cell polarity is required in cardiac progenitor cells for normal outflow tract morphogenesis, site of 40% of CHD.
These exciting findings point to progenitor cell polarity as a being a major research focus in the etiology of common forms of CHD.




Novel biology of congenital heart defects

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.