Full text
| |
| Author(s): |
Patricia Helena Gilberto Rios Pereira
Total Authors: 1
|
| Document type: | Master's Dissertation |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) |
| Defense date: | 2009-12-18 |
| Examining board members: |
Edna Regina Nakandakare;
Eliana Cotta de Faria;
Rosa Ferreira dos Santos
|
| Advisor: | Edna Regina Nakandakare |
| Abstract | |
The development of atherosclerosis in type 2 diabetes mellitus (DM2) is associated with lipoprotein (LP) modifications. Glycoxidized LDL increases macrophage cholesterol accumulation whereas HDL modifications impair the reverse cholesterol transport and atheroprotective properties. The objective of this study was to evaluate the cholesterol content of mouse peritoneal macrophage (MPM) after their simultaneous incubation with LDL+HDL or LDL alone from poorly controlled DM2 (D, n=11), and from non-diabetic control individuals (C, n=11). LP were isolated by discontinuous density gradient ultracentrifugation and incubated (100g protein/mL) with MPM (48h), according to the following protocol: LDL(C); LDL(C)+HDL(C); LDL(C)+HDL(C) pool; LDL(D); LDL(D)+HDL(D) or LDL(D)+ HDL(C) pool. The cellular contents of free (FC) and of esterified cholesterol (EC: linoleate, oleate and palmitate) were measured by HPLC (g/mg of cell protein). Age, BMI, fasting plasma glucose, HbA1c and triglycerides were higher in D as compared to C. The incubation with LDL(D)+HDL(D) increased MCM TC (mean ± SEM) (607 ± 99; p = 0,033) and EC (430 ± 86; p = 0,023) contents compared to LDL(D) alone (356 ± 73; 209 ± 51, respectively). Also, MPM EC content was higher compared to LDL(D)+HDL(C)pool (208 ± 70; p = 0,023). MPM incubated with LDL(D)+HDL(D) presented greater contents of TC (607 ± 99; p = 0,01), FC (177 ± 21; p = 0,03) and of EC (430 ± 86; p = 0,02) compared to the LDL(C)+HDL(C)pool (266 ± 66, 89 ± 16 e 176 ± 53, respectively). The cellular EC content was ascribed to accumulations of linoleate and oleate. Analysis of the HDL composition showed higher lipid/apo A-I ratio in HDL(D) compared to HDL(C). In conclusion, the simultaneous incubation of LDL(D)+HDL(D) induces greater cholesterol accumulation in macrophage compared to LDL(D) and LDL(C)+HDL(C)pool. These results suggest that uncontrolled DM2 HDL favours the cellular cholesterol accumulation. (AU) | |