Inter- and Intracellular Signaling Pathways
Congenital heart disease arises from defects during prenatal heart development. This process is coordinated through a complicated web of intercellular communication between the epicardium, the endocardium, and the myocardium. In the postnatal heart, simil
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Jörg Heineke
Contents 11.1 Introduction 11.2 Intercellular Signaling in Cardiac Development and Physiological Growth 11.2.1 Endocardial-Myocardial Signaling 11.2.2 Myocardial-Endocardial Signaling 11.2.3 Epicardial-Myocardial Signaling 11.2.4 Myocardial-Epicardial Signaling 11.3 Intercellular Signaling During Pathological Cardiac Growth 11.3.1 Communication Between Cardiomyocytes 11.3.2 Endothelial-Cardiomyocyte Crosstalk 11.3.3 Fibroblast-Cardiomyocyte Crosstalk 11.4 Cardiomyocyte Intracellular Signaling During Pathological and Physiological Heart Growth 11.4.1 Signaling in Physiological Heart Growth 11.4.2 Signaling in Pathological Heart Growth Conclusion References
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Abstract
Congenital heart disease arises from defects during prenatal heart development. This process is coordinated through a complicated web of intercellular communication between the epicardium, the endocardium, and the myocardium. In the postnatal heart, similar crosstalk between cardiomyocytes, endothelial cells, and fibroblasts exists during pathological hemodynamic overload that emerges as a consequence of a congenital heart defect. Ultimately, communication between
J. Heineke Experimentelle Kardiologie, Rebirth – Cluster of Excellence, Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Hannover, Germany e-mail: [email protected] © Springer-Verlag Wien 2016 S. Rickert-Sperling et al. (eds.), Congenital Heart Diseases: The Broken Heart: Clinical Features, Human Genetics and Molecular Pathways, DOI 10.1007/978-3-7091-1883-2_11
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cells triggers the activation of select intracellular signaling circuits to mediate hypertrophy in cardiac myocytes. Here, I review the inter- and intracellular signaling mechanisms in the heart as they were discovered mainly in genetically modified mice. The hope is that in the future, targeted therapy of specific molecules or cascades will allow correction of defects that lead to the development of congenital heart disease or pathological hypertrophy.
11.1
Introduction
Signaling between different cell types of the heart coordinates the complex events of cardiac development that finally result in the functioning four-chambered heart. Specific growth factors are released from a particular cell type at a given time point in development to direct and control the differentiation, proliferation, or migration of one or multiple neighboring cell types. In this manner, endocardial cells release, for example, neuregulin1 to induce trabeculation and proliferation of the adjacent myocardium. Similar signaling circuits originate from cardiomyocytes to impact endocardial cells and also exist between epicardial cells and the myocardium. Defects in these events (e.g., as a consequence of an inherited gene mutation) are a common reason for congenital heart disease. On the other hand, the existence of congenital heart disease puts an extra burden (i.e., pressure or volume overload) on the right or left ventricle
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