Role of COUP-TFII in the expression profile of Sca1+ cardiac progenitor cells

• Κύριος συγγραφέας: Αϊβαλιώτη, Μαρία
• Άλλοι συγγραφείς: Φλυτζάνης, Κωνσταντίνος
• Μορφή: Thesis
• Γλώσσα: English
• Έκδοση: 2016
• Θέματα: COUP-TFII; Overexpression; Silencing; Sca1+ cardiac progenitor cells; Marker genes expression profile; Υπερέκφραση; Αποσιώπηση; Sca1+ καρδιακά προγονικά κύτταρα; Προφίλ έκφρασης μορίων-δεικτών; 616.120 607 24

Cardiovascular disease which include myocardial infarction and chronic cardiomyopathies, among others, consist the major cause of death worldwide, according to the World Health Organization reports ( www.who.int/en/ ). The capacity of heart repair is minimal because postnatal cardiomyocytes do not proliferate.Cardiovascular diseases lead to loss of functional cardiac tissue which is replaced by fibrous tissue that has no contraction capacity. The functionality of the myocardium can be reduced to such an extent that, in most cases, the patients are led to heart failure and even death. Till today, heart transplantation, which poses many risks, constitutes the only effective treatment of heart failure. New studies seem to pave the way for new therapeutical approaches, such as the use of induced Pluripotent Stem Cells (iPSCs) and direct reprogramming of cardiac fibroblasts towards cardiomyocytes (Masaki et. al., 2010). The discovery of Cardiac Progenitor Cells (CPCs) with stem cell properties in the adult myocardium, constitute a great achievement for the development of new therapeutical methods to be used in the treatment and cure of heart disease. A lot of effort has been put for the identification of key molecules with crucial role in developmental pathways and differentiation potential of cardiac progenitor cells. In the present study we focused on the nuclear receptor Chicken Ovalbumin Upstream Promoter Transcription factor II (COUP-TFII), which can be considered a key molecule, since it has been well documented that COUP-TFII serves as one of the master regulators to control a variety of developmental programs, including organogenesis, angiogenesis, cardiovascular development, reproduction, neuronal development and metabolic homeostasis (Qin et al, 2014). Specifically, we studied the COUP-TFII overexpression and silencing effects in the character and marker genes expression profile in Sca1+ cardiac progenitor cells. Initially, a molecular profile analysis of Sca1+ cardiac progenitor cells was performed and indicated that apart from cardiac progenitor cell markers, they also express endothelial progenitor cell markers, consistent with the literature (Galvez et al. 2008). COUP-TFII overexpression showed that this factor may promote differentiation of Sca1+ cells towards venous endothelial cells, since they seem to alter their CPCs molecular expression profile, presenting a predisposition for entering the venous endothelial cell lineage. Notably, in COUP-TFII overexpressing Sca1+ cells, Hey2, a downstream effector of Notch Signaling, was suppressed, while Angiopoietin-1 expression, which is required for angiogenesis of venous endothelial cells, was induced. On the other hand, in the absence of COUP-TFII, the character of Sca1+ cells did not seem to be altered, suggesting that basal expression levels of COUP-TFII may be important for Sca1+ cardiac progenitor or venous endothelial progenitor cells maintenance.