Event Title
Novel Contributions of an Extracellular Matrix Molecule to Coronary Vessel Formation
Location
Philadelphia
Start Date
3-5-2017 1:00 PM
Description
Introduction: Coronary vascular anomalies occur in ~1% of the population and lead to myocardial ischemia, infarction and heart failure. Identification of molecular signals and cell origins of coronary vascular smooth muscle and endothelial cells during coronary vasculogenesis are key to understanding these anomalies. The proepicardium (PE) gives rise to the epicardium and 20% of epicardial-derived cells (EPDCs) that subsequently differentiate into coronary vascular endothelial cells via regulation by transcription factors like Tbx5. PE-specific deletion of Tbx5 impairs epicardium and coronary vessel formation in embryonic mouse hearts and reduces expression of Reln mRNA that encodes the Reelin extracellular matrix glycoprotein. Reelin regulates cell migration and positioning in neuronal and lymphatic vascular cells, but its role in cardiovascular development is unknown. Methods: Thus, we sought to identify functional contributions of Reelin to structural formation of the developing mammalian heart. Using multiple approaches, we (1) analyzed the ability of TBX5 to regulate RELN transcription via promoter interactions in human lung epithelial cells that stably express TBX5, (2) examined the spatiotemporal pattern of Reelin expression in embryonic and adult mouse hearts via immunofluorescent staining with cell lineage-specific markers, and (3) explored the functional contribution of Reelin to endothelial tubule formation in primary human microvascular endothelial cells (HMECs) that serve as an in vitro model of vasculogenesis. Results: We demonstrate that TBX5 activates RELN transcription. Reelin is expressed in the PE and epicardium as well as nascent and mature coronary vessels of embryonic mouse hearts. Its expression is maintained in adult heart coronary vessels. RELN gene-silencing alters formation of HMECs into the endothelial tubule precursors of coronary vessels. Conclusion: Reelin provides an integral contribution to formation of coronary vessels.
Novel Contributions of an Extracellular Matrix Molecule to Coronary Vessel Formation
Philadelphia
Introduction: Coronary vascular anomalies occur in ~1% of the population and lead to myocardial ischemia, infarction and heart failure. Identification of molecular signals and cell origins of coronary vascular smooth muscle and endothelial cells during coronary vasculogenesis are key to understanding these anomalies. The proepicardium (PE) gives rise to the epicardium and 20% of epicardial-derived cells (EPDCs) that subsequently differentiate into coronary vascular endothelial cells via regulation by transcription factors like Tbx5. PE-specific deletion of Tbx5 impairs epicardium and coronary vessel formation in embryonic mouse hearts and reduces expression of Reln mRNA that encodes the Reelin extracellular matrix glycoprotein. Reelin regulates cell migration and positioning in neuronal and lymphatic vascular cells, but its role in cardiovascular development is unknown. Methods: Thus, we sought to identify functional contributions of Reelin to structural formation of the developing mammalian heart. Using multiple approaches, we (1) analyzed the ability of TBX5 to regulate RELN transcription via promoter interactions in human lung epithelial cells that stably express TBX5, (2) examined the spatiotemporal pattern of Reelin expression in embryonic and adult mouse hearts via immunofluorescent staining with cell lineage-specific markers, and (3) explored the functional contribution of Reelin to endothelial tubule formation in primary human microvascular endothelial cells (HMECs) that serve as an in vitro model of vasculogenesis. Results: We demonstrate that TBX5 activates RELN transcription. Reelin is expressed in the PE and epicardium as well as nascent and mature coronary vessels of embryonic mouse hearts. Its expression is maintained in adult heart coronary vessels. RELN gene-silencing alters formation of HMECs into the endothelial tubule precursors of coronary vessels. Conclusion: Reelin provides an integral contribution to formation of coronary vessels.