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| Author(s): |
André Fonseca Alves
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) |
| Defense date: | 2002-04-09 |
| Examining board members: |
Ligia Ferreira Gomes;
Francisco Antônio Helfenstein Fonseca;
Adelaide Jose Vaz
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| Advisor: | Ligia Ferreira Gomes |
| Abstract | |
Advanced age and dislipidemic disorders are two of the main risk factors in the development of cardiovascular disease, as they are associated to the physiopathology of atherosclerosis. In vivo LDL oxidation is involved both in the initiation mechanism and the progression of atheroma plaques. Oxidized LDL, found in the subendothelial space, interferes in endothelial cell and macrophage function . A minimally oxidized form of LDL, called LDLminus, is also found in the blood stream. The importance of antioxidant vitamins in the in vivo protection of the particle is currently a matter of discussion; indeed, its susceptibility to in vitro oxidation depends on its lipossoluble antioxidant content. Apolipoprotein H, also known as β2-glycoprotein I (β2- GPI), is a molecule capable of binding to in vitro oxidized lipoproteins, particularly to oxidized LDL, and may play a protective role in vivo. LDL oxidation evaluated by its susceptibility to in vitro oxidation and the in vivo plasmatic concentration of LDLminus -, as well as plasmatic concentration of antioxidant vitamins and of β2GPI , were assessed in one hundred elderly hypercholesterolemic (LDL concentration > 130mg/dL) subjects, otherwise clinically normal. These subjects received nutritional orientation to follow the diet recommended by the American Heart Association, as well as to perform regular physical activities. Total cholesterol and its fractions were measured and the LDL fraction was subsequently separated by ultracentrifugation in order to determine its susceptibility to oxidation and the concentration of LDLminus in the fraction. The extension of the lag phase during oxidability assays was found to be of 68 ± 23 min, with an oxidation rate of 0,03 ± 0,01 Abs/min. Plasmatic concentration of LDLminus was 8 ± 6 mg/dL, corresponding to 5 ± 3% of the native LDL. Following HPLC separation, plasmatic concentration of ascorbic acid (57 ± 23 µM), β-carotene (0,4 ± 0,3 nmol/mg LoL cholesterol), Iycopene (0,4 ± 0,2 nmol/mg LDL cholesterol), α-tocopherol (11 ± 4 nmollmg LDL cholesterol), γ-tocopherol (1,8 ± 0,9 nmollmg LDL cholesterol), and ubiquinol-10 (0,09 ± 0,07 nmol/mg LDL cholesterol) were determined. A competition immune enzymatic assay was standardized to measure β2GPI plasmatic concentration, which was found to be 397 ± 168 µg/mL. LDLminus concentration inversely correlates to both α-tocopherol (p=0,003) and ubiquinol-10 (p=0,046) plasmatic contents. Also, ubiquinol-10 directly correlates to the lag phase of the oxidability assay (p=0,037). These results support the contention that α-tocopherol and ubiquinol-10 protect LDL from oxidation. Moreover, the increased plasmatic concentrations of β2GPI found in the hypercholesterolemic elderly subjects suggest the involvement of this glycoprotein in the metabolism of lipoproteins. (AU) | |