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Long-term dietary nitrate supplementation slows the progression of established atherosclerosis in ApoE-/- mice fed a high fat diet.
Liu, Yang; Croft, Kevin D; Mori, Trevor A; Gaspari, Tracey A; Kemp-Harper, Barbara K; Ward, Natalie C.
Afiliación
  • Liu Y; School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.
  • Croft KD; School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.
  • Mori TA; Medical School, University of Western Australia, Perth, WA, Australia.
  • Gaspari TA; Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
  • Kemp-Harper BK; Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
  • Ward NC; Medical School, University of Western Australia, Perth, WA, Australia. natalie.ward@uwa.edu.au.
Eur J Nutr ; 62(4): 1845-1857, 2023 Jun.
Article en En | MEDLINE | ID: mdl-36853380
BACKGROUND AND AIMS: Atherosclerosis is associated with a reduction in the bioavailability and/or bioactivity of endogenous nitric oxide (NO). Dietary nitrate has been proposed as an alternate source when endogenous NO production is reduced. Our previous study demonstrated a protective effect of dietary nitrate on the development of atherosclerosis in the apoE-/- mouse model. However most patients do not present clinically until well after the disease is established. The aims of this study were to determine whether chronic dietary nitrate supplementation can prevent or reverse the progression of atherosclerosis after disease is already established, as well as to explore the underlying mechanism of these cardiovascular protective effects. METHODS: 60 apoE-/- mice were given a high fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis. The mice were then randomized to (i) control group (HFD + 1 mmol/kg/day NaCl), (ii) moderate-dose group (HFD +1 mmol/kg/day NaNO3), or (iii) high-dose group (HFD + 10 mmol/kg/day NaNO3) (20/group) for a further 12 weeks. A group of apoE-/- mice (n = 20) consumed a normal laboratory chow diet for 24 weeks and were included as a reference group. RESULTS: Long-term supplementation with high dose nitrate resulted in ~ 50% reduction in plaque lesion area. Collagen expression and smooth muscle accumulation were increased, and lipid deposition and macrophage accumulation were reduced within atherosclerotic plaques of mice supplemented with high dose nitrate. These changes were associated with an increase in nitrite reductase as well as activation of the endogenous eNOS-NO pathway. CONCLUSION: Long-term high dose nitrate significantly attenuated the progression of established atherosclerosis in the apoE-/- mice fed a HFD. This appears to be mediated in part through a XOR-dependent reduction of nitrate to NO, as well as enhanced eNOS activation via increased Akt and eNOS phosphorylation.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Aterosclerosis / Placa Aterosclerótica Tipo de estudio: Clinical_trials Límite: Animals Idioma: En Revista: Eur J Nutr Asunto de la revista: CIENCIAS DA NUTRICAO Año: 2023 Tipo del documento: Article País de afiliación: Australia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Aterosclerosis / Placa Aterosclerótica Tipo de estudio: Clinical_trials Límite: Animals Idioma: En Revista: Eur J Nutr Asunto de la revista: CIENCIAS DA NUTRICAO Año: 2023 Tipo del documento: Article País de afiliación: Australia