Disturbed flow induces systemic changes in metabolites in mouse plasma: a metabolomics study using ApoEâ»/â» mice with partial carotid ligation.
Am J Physiol Regul Integr Comp Physiol
; 308(1): R62-72, 2015 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-25377480
ABSTRACT
Disturbed blood flow (d-flow) occurring in branched and curved arteries promotes endothelial dysfunction and atherosclerosis, in part, by altering gene expression and epigenomic profiles in endothelial cells. While a systemic metabolic change is known to play a role in atherosclerosis, it is unclear whether it can be regulated by local d-flow. Here, we tested this hypothesis by carrying out a metabolomics study using blood plasma samples obtained from ApoE(-/-) mice that underwent a partial carotid ligation surgery to induce d-flow. Mice receiving sham ligation were used as a control. To study early metabolic changes, samples collected from 1 wk after partial ligation when endothelial dysfunction occurs, but before atheroma develops, were analyzed by high-resolution mass spectrometry. A metabolome-wide association study showed that 128 metabolites were significantly altered in the ligated mice compared with the sham group. Of these, sphingomyelin (SM; m/z 703.5747), a common mammalian cell membrane sphingolipid, was most significantly increased in the ligated mice. Of the 128 discriminatory metabolites, 18 and 41 were positively and negatively correlated with SM, respectively. The amino acids methionine and phenylalanine were increased by d-flow, while phosphatidylcholine and phosphatidylethanolamine were decreased by d-flow, and these metabolites were correlated with SM. Other significantly affected metabolites included dietary and environmental agents. Pathway analysis showed that the metabolic changes of d-flow impacted broad functional networks. These results suggest that signaling from d-flow occurring in focal regions induces systemic metabolic changes associated with atherosclerosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
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Biomarcadores
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Artérias Carótidas
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Doenças das Artérias Carótidas
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Estenose das Carótidas
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Metabolômica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Regul Integr Comp Physiol
Assunto da revista:
FISIOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article