Disturbed flow induces systemic changes in metabolites in mouse plasma: a metabolomics study using ApoE −/− mice with partial carotid ligation
Young-Mi Go, Chan Woo Kim, Douglas I. Walker, Dong Won Kang, Sandeep Kumar, Michael Orr, Karan Uppal, Arshed A. Quyyumi et al.. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2015-01-01
Topic: Gut, metabolism and diet
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.
Key findings
- 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.
- 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.
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Study details
- Evidence strengthLow
How this study scored 36/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 20 of the 56 points we could judge it on, which is 36 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (American Journal of Physiology-Regulatory, Integrative and Comparative Physiology) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2015 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “mouse”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 20 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 20 of the 56 points we could judge it on is 36 out of 100. |
| Total | 36 / 100 | — |
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APA 7th
Go, Y.-M., Kim, C. W., Walker, D. I., Kang, D. W., Kumar, S., Orr, M., et al. (2015). Disturbed flow induces systemic changes in metabolites in mouse plasma: a metabolomics study using ApoE −/− mice with partial carotid ligation. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. https://doi.org/10.1152/ajpregu.00278.2014
Vancouver
Go Y.-M, Kim CW, Walker DI, Kang DW, Kumar S, Orr M, et al. Disturbed flow induces systemic changes in metabolites in mouse plasma: a metabolomics study using ApoE −/− mice with partial carotid ligation. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2015. doi:10.1152/ajpregu.00278.2014.
BibTeX
@article{go2015-e136ebd7,
author = {Go, Young-Mi and Kim, Chan Woo and Walker, Douglas I. and Kang, Dong Won and Kumar, Sandeep and Orr, Michael and Uppal, Karan and Quyyumi, Arshed A. and others},
title = {{Disturbed flow induces systemic changes in metabolites in mouse plasma: a metabolomics study using ApoE −/− mice with partial carotid ligation}},
journal = {American Journal of Physiology-Regulatory, Integrative and Comparative Physiology},
year = {2015},
doi = {10.1152/ajpregu.00278.2014},
url = {https://doi.org/10.1152/ajpregu.00278.2014}
}
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