Date of Award
Heparan Sulfate, Endothelial Cells, Atherosclerosis
Atherosclerotic plaque localizes in predictable areas such as arches and bifurcations which are characterized by disturbed flow patterns and the resulting damage and dysfunction to the endothelium. Endothelial cells (ECs) under sustained laminar flow align in the direction of flow; however, under disturbed flow conditions, ECs sustain damage to their glycocalyx (GCX) which results in unaligned and rounder cells. An investigation into the role of NDST1 sulfation of heparan sulfate (HS), a key component of many proteoglycans which make up the GCX, was conducted. The descending aortas (DAs) of transgenic mice with conditional knockouts (KOs) of NDST1 in vascular ECs were quantified for changes in alignment on the basis of: aspect ratio (AR), circularity, and angle of alignment relative to the direction of flow. NDST1 KO animals displayed no significant negative changes in alignment and significant positive changes in one of the three categories measured. To confirm the presence of the HS chain backbone, cross sections of vessels were stained for sulfation sites directed by the NDST1 or HS3ST1 enzymes. NDST1 or HS3ST1 sulfation. NDST1 KO animals had a significant knockdown of NDST1 sulfation and a normal expression of HS3ST1 sulfation confirming the presence of the HS backbone. This result supported the conclusion that the HS backbone remains intact and functional despite the deletion of NDST1 sulfation.
Diaz de Leon, John III, "Knockdown of Heparan Sulfate Via NDST1 knockout Does Not Inhibit Mouse Aortic Endothelial Cell Alignment In-Vivo" (2018). CUNY Academic Works.