Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Cardiovasc Res ; 117(2): 435-449, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-32267921

RESUMO

AIMS: The microbiome-derived metabolite trimethylamine-N-oxide (TMAO) has attracted major interest and controversy both as a diagnostic biomarker and therapeutic target in atherothrombosis. METHODS AND RESULTS: Plasma TMAO increased in mice on 'unhealthy' high-choline diets and notably also on 'healthy' high-fibre diets. Interestingly, TMAO was found to be generated by direct oxidation in the gut in addition to oxidation by hepatic flavin-monooxygenases. Unexpectedly, two well-accepted mouse models of atherosclerosis, ApoE-/- and Ldlr-/- mice, which reflect the development of stable atherosclerosis, showed no association of TMAO with the extent of atherosclerosis. This finding was validated in the Framingham Heart Study showing no correlation between plasma TMAO and coronary artery calcium score or carotid intima-media thickness (IMT), as measures of atherosclerosis in human subjects. However, in the tandem-stenosis mouse model, which reflects plaque instability as typically seen in patients, TMAO levels correlated with several characteristics of plaque instability, such as markers of inflammation, platelet activation, and intraplaque haemorrhage. CONCLUSIONS: Dietary-induced changes in the microbiome, of both 'healthy' and 'unhealthy' diets, can cause an increase in the plasma level of TMAO. The gut itself is a site of significant oxidative production of TMAO. Most importantly, our findings reconcile contradictory data on TMAO. There was no direct association of plasma TMAO and the extent of atherosclerosis, both in mice and humans. However, using a mouse model of plaque instability we demonstrated an association of TMAO plasma levels with atherosclerotic plaque instability. The latter confirms TMAO as being a marker of cardiovascular risk.


Assuntos
Aterosclerose/sangue , Bactérias/metabolismo , Colina/administração & dosagem , Dieta Saudável , Fibras na Dieta/administração & dosagem , Microbioma Gastrointestinal , Metilaminas/sangue , Placa Aterosclerótica , Ração Animal , Animais , Aterosclerose/diagnóstico por imagem , Aterosclerose/microbiologia , Aterosclerose/patologia , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/microbiologia , Colina/metabolismo , Colina/toxicidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/microbiologia , Fibras na Dieta/metabolismo , Modelos Animais de Doenças , Disbiose , Fatores de Risco de Doenças Cardíacas , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Receptores de LDL/genética , Receptores de LDL/metabolismo , Ruptura Espontânea , Calcificação Vascular/sangue , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/microbiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA