Avaliação da deposição de placa aterosclerótica e disfunção vascular em aorta de camundongos ApoE-/- após exposição crônica ao cádmio
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Data
2018-04-12
Autores
Oliveira, Thiago Fernandes de
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Universidade Federal do Espírito Santo
Resumo
Introduction: Cadmium exposure is related to cardiovascular diseases, including hypertension and atherosclerosis, which are linked to oxidative stress induced by this metal. Objective: the present study investigated whether the exposure to cadmium promotes the formation of atherosclerotic plaque and promotes endothelial dysfunction in the aorta, in addition to oxidative stress in knockout mice for lipoprotein E (ApoE-/- ). Methods: Experiments were performed on 14 week-old male C57BL / 6 and ApoE-/- mice treated with cadmium chloride (100 mg / L CdCl2 in drinking water for 28 days) or vehicle (distilled water). After exposure to the metal a cholesterol dosage was made and vascular reactivity in response to phenylephrine, acetylcholine or sodium nitroprusside were analysed in the isolated aorta. Bone marrow cells were isolated to evaluate the production of nitric oxide and reactive species of oxygen and nitrogen and the atherosclerotic plaque in the aortic arch was measured. Result: ApoE-/- mice exposed to cadmium showed higher levels of cholesterol than the animals that were not exposed. Cadmium exposure reduced acetylcholine induced relaxation in ApoE-/- , although it did not alter the responses elicited by phenylephrine or sodium nitroprusside. L-NAME incubation reduced the vasodilator response to acetylcholine, but this effect was smaller in cadmium treated ApoE-/- mice, suggesting a reduction in nitric oxide bioavailability. In addition, in cells hematopoietic, cadmium decreased cytoplasmic levels of nitric oxide and increased superoxide anion, hydrogen peroxide and peroxynitrite in ApoE-/- mice exposed to cadmium. Morphological analysis showed that cadmium-treated ApoE-/- mice exhibited increased plaque deposition in the aorta by approximately 3-fold comparing to the non-treated ApoE-/- mice. Conclusion: our results suggest that a cadmium exposure induces endothelial dysfunction in ApoE-/- mice. In addition, cadmium increased cholesterol plasmatic levels, which may promote the development of atherosclerosis in the aorta of ApoE-/- mice. Our findings support a hypothesis that the exposure to cadmium may increase the risk of atherosclerosis development.
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Cadmium , Atherosclerosis , Endothelial dysfunction , Oxidative stress , Aterosclerose , Disfunção endotelial , Estresse oxidativo
Citação
OLIVEIRA, Thiago Fernandes de. Avaliação da deposição de placa aterosclerótica e disfunção vascular em aorta de camundongos ApoE-/- após exposição crônica ao cádmio. 87 f. Dissertação (Mestrado em Ciências Fisiológicas) - Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Espírito Santo, Vitória, 2018.