The goal of this thesis was to elucidate the physicochemical and metabolic bases of Hyperapobetalipoproteinemia (HyperapoB). This disorder, which is likely the commonest metabolic abnormality associated with premature coronary artery disease, was defined as a combination of a normal, or near-normal, LDL cholesterol in the face of an elevated LDL apoB. / LDL, even in normals, is heterogeneous. The experimental findings herein confirm this. They also extend this concept to indicate that familial hypercholesterolemia (FH) and HyperapoB each imprint LDL in different and characteristic ways, each an exaggeration of the typical relations between LDL composition and size in normals. At one extreme is HyperapoB, which is characterized by most of the LDL particles being smaller and denser than normal because they contain less cholesteryl ester but the same amount of apoB as normal. At the other is FH, which is characterized by larger, cholesteryl ester-enriched particles. There is, as well, a predictable relation between LDL particle size and the immunoreactivity of certain apoB epitopes. / Turnover studies of hepatic apoB using traditional analytic models showed that hepatic apoB is overproduced in HyperapoB, a finding which stands in marked contrast to the impaired catabolism of apoB in FH. A new multi-compartmental model of LDL metabolism has been developed which appears to elucidate several of the basic mechanisms involved in the pathogenesis of HyperapoB. All the data to date indicate that the characteristic abnormalities of LDL in HyperapoB are all consequences of the overproduction of hepatic apoB. Obviously, the goal for future research must be to understand the basis for this overproduction. A preliminary study with adipose tissue suggested that the overproduction of hepatic apoB might be secondary to a defect in peripheral tissue triglyceride biosynthesis.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.74368 |
| Date | January 1987 |
| Creators | Teng, Ba-Bie. |
| 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 (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000420043, proquestno: AAINN66344, Theses scanned by UMI/ProQuest. |
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