A terapia com células mononucleares atenua a aterosclerose em camundongos ApoE Knockout

• Autor(a) principal: Porto, Marcella Leite
• Data de Publicação: 2011
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/7964
• topic: Fisiologia; 612

Cardiovascular diseases are leading causes of morbidity and mortality worldwide. Among these, there is atherosclerosis, a chronic inflammatory disease of the arterial wall. Despite conventional therapies (pharmacological or surgical interventions) are of great value, cell therapy emerges as a new therapeutic strategy for treating and preventing atherosclerosis. Thus, the aim of this study was to evaluate the effects of mononuclear cell (MNC) therapy on the development of atherosclerotic lesions in the apolipoprotein E knockout (apoE KO) mouse. ApoE KO female mice (24-week-old) were randomly divided into two groups: 1) an apoE KO control group (n = 8) and 2) an apoE KO group that received MNC therapy (apoE KO-MNC, n = 8). β-galactosidase (β-gal) (encoded by the lacZ gene) transgenic mice (12-week-old) were used as MNC donors. Six-month-old apoE KO mice were fed a cholesterol-rich diet (1.25% cholesterol) for 4 to accelerate the process of atherogenesis. ApoE KO-MNC received mononuclear cells isolated from the spleen of lacZ mice (106 cells / week) for 8 weeks. After euthanasia, a blood sample was collected and the plasma total cholesterol was measured. The aorta was removed for immunohistochemical analysis. We investigated vascular lipid deposition, vascular remodeling, oxidative stress, endothelial nitric oxide synthase (eNOS) expression and the presence of endothelial progenitor cells. in apoE KO mice treated with spleen MNCs isolated from lacZ transgenic mice (apoE KO-MNC) compared to untreated control mice (apoE KO). Data are presented as the mean ± SEM. Statistical analysis was performed with Student’s t-test for independent samples or one-way analysis of variance (ANOVA). Statistical significance was set at p < 0.05. Histological analysis of aortas showed a significant reduction in the lipid deposition area in apoE KO-MNC mice compared to apoE KO mice (0.051 ± 0.004 vs 0.117 ± 0.016 mm2, respectively, p < 0.01). In addition, vessel morphometry revealed that MNC therapy prevented the outward (positive) remodeling in apoE KO mice that is normally observed (apoE KO-MNC: 0.98 ± 0.07 vs apoE KO: 1.37 ± 0.09), using wildtype mice (C57BL/6J) as a reference. ApoE KO-MNC mice also have reduced 15 production of superoxide anions and increased eNOS expression compared to apoE KO mice. Finally, immunohistochemistry analysis revealed a homing of endothelial progenitor cells (EPCs) in the aortas of apoE KO-MNC mice. We concluded that MNC therapy attenuates the progression of atherosclerosis in the aortas of apoE KO mice. Our data provide evidence that the mechanism by which this attenuation occurs includes the homing of EPCs, a decrease in oxidative stress and an upregulation of eNOS expression.