Plasma acylation stimulating protein (ASP) is a small basic protein isolated from human plasma that stimulates triglyceride synthesis (TGS) and glucose transport (GT) in human skin fibroblasts and adipocytes. ASP was measured in fasting samples of 59 age-matched controls and 208 patients with documented coronary artery, disease (CAD). Overall, plasma ASP was higher in the CAD patients than in the controls and within the CAD patients, plasma ASP was highest in the group that had neither an FHTG-type (hypertriglyceridemic normal apoB) nor an FH-type (marked hypercholesterolemia and apoB with normal plasma triglyceride) phenotype. The relations between plasma ASP, triglyceride rich lipoproteins and apoB in the remaining CAD subjects were examined and ASP increased with either increasing triglyceride or apoB. In 208 CAD subjects, 47 subjects had ASP greater than 95th percentile (greater than 65 nM). Within those 47 subjects, 66% had increased plasma apoB (apoB > 105mg/dl). / The relationship between ASP and hyperapoB (apoB > 105mg/dl) was further investigated in cell culture study. Human skin fibroblasts were obtained from normals and hyperapoB patients. The fibroblasts from the three groups of subjects (normal subjects:NASP-NB, hyperapoB subjects with normal plasma ASP:NASP-HB, and hyperapoB subjects with high plasma ASP:HASP-HB) were studied for TGS and GT in response to ASP, PMA (4beta phorbol 12-myristate 13-acetate, a protein-kinase C stimulator) and insulin stimulation. The competition binding of 125I ASP to the fibroblasts from the three groups of subjects was also examined. / The data showed that only HASP-HB cells have a lower response to ASP in TGS and GT. The responses to insulin and PMA in TGS and GT are normal. There is no significant difference among the three groups in the Kd values (NASP-NB Kd: 163 +/- 23nM) for binding to 125I ASP. The Bmax value for the H ASP-HB group is 50% lower than the other two groups (N ASP-NB:NASP-HB:HASP-H B: 334 +/- 81:427 +/- 92:146 +/- 33 pmoles/mg cell protein). / The reduced receptor of ASP on the cell surface of HASP-H B patients can lead to the reduced response to ASP.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.35493 |
| Date | January 1999 |
| Creators | Zhang, Xiaojing, 1967- |
| Contributors | Cianflone, Katherine (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 (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001652506, proquestno: NQ50285, Theses scanned by UMI/ProQuest. |
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