Insight into cardiac development is bound to have a direct impact on our understanding of human heart disease in many ways. Recent studies point to the importance of the transactivation of cardiac control genes, which are stress-responsive regulators of gene expression during both postnatal heart development and heart failure progression. Based on the results of our research, we have targeted three fetal control genes, which are redeployed in the postnatal heart in response to stress signals that can provoke cardiac dysfunction and heart failure: (1) cardiac ankyrin repeat domain 1 protein (ANKRD1), (2) myocardin, and (3) homeo-domain only protein (Hop). Using a minimally-invasive model of experimentally controlled cardiomyopathic propagation in neonatal piglets in combination with expression display analyses, we have demonstrated the augmentation of the ANKRD1 and myocardin transcript and protein, not only during postnatal cardiac development, but also in failing myocardium. We additionally extended the clinical significance of this work by detecting augmented ANKRD1 and myocardin levels in cardiac samples obtained from patients with end-time cardiomyopathies. We also showed that expression of Hop, an antagonist of myocardin activity, is diminished in human failing myocardium. Our goal is also to identify common pathways in the developmental networks of these genes that can be reproduced in normal and cardiomyopathic settings in the postnatal heart. It is intriguing to speculate on how the transcription of ANKRD1, myocardin and Hop become permissible in postnatal hearts and how it can be influenced by physiological and pathological signaling.
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