Submitted on December 19, 2007
Revised on February 5, 2008
Accepted on March 7, 2008
Transcription Repression and Blocks in Cell Cycle Progression in Hypoplastic Left Heart Syndrome
Katheryn Gambetta1, Mohamad K Al-Ahdab2, Michel N Ilbawi2, Nahidh Hassaniya3, and Madhu Gupta4*
1 The Heart Institute for Children
2 Hope Childrens Hospital
3 Loma Linda University
4 Rush University Medical Center
* To whom correspondence should be addressed. E-mail: gupta{at}thic.com.
Hypoplastic Left Heart Syndrome (HLHS) is characterized by abnormally developed atrial septum and severe underdevelopment of the left side of the heart. Despite significant advances in its surgical management, little is known about the molecular abnormalities in this syndrome. To gain molecular insights into HLHS, expression profiling by gene chip microarray (Affymetrix U133 2.0) and by real-time RT-PCR was performed in the atrial septum of patients diagnosed with HLHS and compared to age-matched non-HLHS patients. Hierarchical clustering of all expressed genes with a p<0.01 of all tissue samples showed two main clusters, one of HLHS and the other of non-HLHS, suggesting different expression patterns by the two groups. Net-affix followed by real-time RT-PCR analysis identified the differentially expressed genes to be those involved in chromatin remodeling, in cell cycle regulation and in transcriptional regulation. These included remodeling factors, HDAC2 and SYMD1; transcription factors, Fox P1, and components of Calcineurin-NFATc signaling pathway; and cell cycle regulators, CDK-4, PTEN and p18. Since these factors play essential roles in heart growth and development, the abnormal expression pattern suggest that these molecules may contribute to the pathogenesis of HLHS.
