| Texto completo | |
| Autor(es): |
Dorighello, Gabriel G.
;
Rovani, Juliana C.
;
Paim, Bruno A.
;
Rentz, Thiago
;
Assis, Leandro H. P.
;
Vercesi, Anibal E.
;
Oliveira, Helena C. F.
Número total de Autores: 7
|
| Tipo de documento: | Artigo Científico |
| Fonte: | JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS; v. 29, n. 6, p. 14-pg., 2022-01-01. |
| Resumo | |
Aim: Atherosclerosis is responsible for high morbidity and mortality rates around the world. Local arterial oxidative stress is involved in all phases of atherosclerosis development. Mitochondria is a relevant source of the oxidants, particularly under certain risky conditions, such as hypercholesterolemia. The aim of this study was to test whether lowering the production of mitochondrial oxidants by induction of a mild uncoupling can reduce atherosclerosis in hypercholesterolemic LDL receptor knockout mice. Methods: The mice were chronically treated with very low doses of DNP (2,4-dinitrophenol) and metabolic, inflammatory and redox state markers and atherosclerotic lesion sizes were determined. Results: The DNP treatment did not change the classical atherosclerotic risk markers, such as plasma lipids, glucose homeostasis, and fat mass, as well as systemic inflammatory markers. However, the DNP treatment diminished the production of mitochondrial oxidants, systemic and tissue oxidative damage markers, peritoneal macrophages and aortic rings oxidants generation. Most importantly, development of spontaneous and dietinduced atherosclerosis (lipid and macrophage content) were significantly decreased in the DNP-treated mice. In vitro, DNP treated peritoneal macrophages showed decreased H2O2 production, increased anti-inflammatory cytokines gene expression and secretion, increased phagocytic activity, and decreased LDL-cholesterol uptake. Conclusions: These findings are a proof of concept that activation of mild mitochondrial uncoupling is sufficient to delay the development of atherosclerosis under the conditions of hypercholesterolemia and oxidative stress. These results promote future approaches targeting mitochondria for the prevention or treatment of atherosclerosis. (AU) | |
| Processo FAPESP: | 17/17728-8 - Função e disfunção mitocondrial: implicações para o envelhecimento e doenças associadas |
| Beneficiário: | Aníbal Eugênio Vercesi |
| Modalidade de apoio: | Auxílio à Pesquisa - Temático |
| Processo FAPESP: | 13/07607-8 - CMPO - Centro Multidisciplinar de Pesquisa em Obesidade e Doenças Associadas |
| Beneficiário: | Licio Augusto Velloso |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |
| Processo FAPESP: | 17/02903-9 - Papel da expressão de CETP no estado redox de macrófagos: possível relevância para inflamação e aterosclerose |
| Beneficiário: | Gabriel de Gabriel Taffarello Dorighello |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 14/02819-0 - Estudo das alterações do metabolismo glicídico e lipídico em modelo com deficiência da transidrogenase de nucleotídeo de nicotinamida mitocondrial (NNT). |
| Beneficiário: | Juliana Cristine Rovani Rodrigues |
| Modalidade de apoio: | Bolsas no Brasil - Doutorado |
| Processo FAPESP: | 09/53762-0 - Estudo da bioenergetica mitocondrial de linfocitos durante o processo de ativacao linfocitaria e de desenvolvimento de lesoes ateroscleroticas |
| Beneficiário: | Bruno Alves Paim |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |
| Processo FAPESP: | 17/03402-3 - Estudo da associação de membranas mitocondriais e de retículo endoplasmático em macrófagos no contexto de hipercolesterolemia: possível relevância para aterosclerose |
| Beneficiário: | Leandro Henrique de Paula Assis |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |