BME MS Thesis Presentation: Samantha Cocchiaro Endothelial Glycocalyx-Dependent Expression of Endothelin-1 and Endothelin Receptor B

Abstract:  Endothelin-1 (ET-1) plays a significant role in many cardiovascular-related conditions such as hypertension, and atherosclerosis. ET-1 is produced by endothelial cells (EC) and secreted into the extracellular space to bind to either endothelial B receptor (ETB) on EC or the endothelial A receptor on smooth muscle cells. Reports suggest that the expression of ET-1 is shear stress magnitude and time-dependent and that the disruption of cytoskeletal structures could mediate the shear stress-induced production of ET-1. The endothelial glycocalyx (GCX) which is a mechanotransducer and is located in close proximity to ETB and is also firmly rooted in the EC membrane through its core proteins could co-participate in the release of ETI during disease. With the use of immunofluorescence staining, enzymes that target specific GCX components and micro-fluidic technology, we defined the role of shear forces and the GCX in the expression of ET-1 and its receptor ETB on the surface of human lung microvascular endothelial cells. Flow trials were 30 minutes long and were done with and without Heparanase III to emulate a degraded glycocalyx. Through this research we found trends that suggests that GCX HS and ETB could be dependent and could co-participate to clear ET-1.