Date of Award
College of Arts and Sciences
Master of Science
Dr. Heather Evans-Anderson
Dr. Laura Glasscock
Dr. Matthew Stern
Cardiomyocyte, Endothelial cell, Heart Development, Myocardial gene regulation, Endocardial-myocardial signaling, FoxO1 transcription factor
The regulation of heart development is an area of research that has important implications for the future treatments of heart injuries. Cardiomyocytes, or cardiac muscle cells, stop proliferating after birth, which limits the adult heart in its ability to repair damaged tissue after injury. The use of targeted therapies to treat heart injury through regenerative mechanisms requires an extremely detailed understanding of the regulatory pathways responsible for directing proliferation of cardiomyocytes during heart development. Interactions between cardiomyocytes in the myocardium with endothelial cells of the endocardium during development are known to occur through cell-cell interactions, including the action of diffusible cell signaling factors. The loss of FoxO1 expression in endothelial cells was shown to disrupt the signaling interactions of endothelial cells and cardiomyocytes (Sengupta et al., 2012) indicating that FoxO1 may be involved in the regulated the signaling pathways between these two cell types. In addition, the growth factors Neuregulin (NRG-1) and IGF-1 are known to mediate the proliferation of cardiomyocytes during heart development (Tian & Morrisey, 2012). FoxO1 has also been shown to regulate many signaling pathways that are involved in controlling cell proliferation, including other growth factor pathways. The purpose of this study was to investigate the role of FoxO1 in endothelial-cardiomyocyte interactions in an in vitro cell co-culture model system to determine if FoxO1 has regulatory roles in cardiomyocyte proliferation via endothelial-myocardial signaling. In this study, we focused on the regulatory role of FoxO1 in NRG-1 expression and the effects of altered NRG-1 expression on the interactions between endothelial cells and cardiomyocytes in the co-culture model. We found that a lack of FoxO1 expression did affect the gene expression of NRG-1, as well as IGF-1 and their respective receptors, ErbB2/ErbB4 and IGF-1R. Interestingly, we also found a difference in the gene expression of our control, depending on whether they were treated with a control siRNA scramble sequence or if they were untreated. A clear understanding of endothelial-cardiomyocyte signaling is essential to further development of therapeutic treatments for cardiovascular defects and disease.
Brown, Taylor, "Role of FOX01 in Endothelial Cell and Cardiomyocyte Signaling" (2016). Graduate Theses. 38.