The injury-induced alterations in sulfated proteoglycans (PG) were studied, in neointima, developed in response to a selective deendothelialization of the aorta, of normocholesterolemic rabbits. Light microscopic radioautography and size exclusion chromatography revealed differences in PG between neointima not covered by regenerated endothelium, and reendothelialized neointima or normal aorta. These differences included radioautographic reaction, concentration, size distribution and composition. Further studies were conducted to examine the putative role of the altered PG in lipoprotein (LP) sequestration and lipid accumulation during atherogenesis. LP-PG complexes were isolated by anti apo-B affinity column, from intima-medial tissues from normal and injured aortas. These complexes contained low density and very low density LP, chondroitin sulfate PG and hyaluronic acid. It appeared that endothelial injury enhanced the formation of LP-PG complexes, particularly in areas covered by regenerated endothelium. The uptake and degradation of LP-PG complexes, derived from normal (LP-NPG) or injured aortas (LP-IPG), by arterial smooth muscle cells (SMC) and blood monocyte-derived macrophages (BMDM) were also examined. LP-PG complexes stimulated LP binding, internalization and degradation by SMC and BMDM. Both cell types showed a higher affinity for LP-IPG than LP-NPG. The uptake of LP-PG complexes was mediated mainly by the LDL receptor pathway and phagocytosis. The scavenger receptor played a minor part in the uptake of LP-PG complexes. Data from this study provide evidence that endothelial injury could trigger alterations in neointimal PG, which in turn, facilitate LP accumulation both extracellularly and intracellularly during atherogenesis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.39812 |
| Date | January 1993 |
| Creators | Ismail, Nermine Ahmed Ehsan |
| Contributors | Alavi, M. Z. (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Pathology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001327693, proquestno: NN87766, Theses scanned by UMI/ProQuest. |
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