Trimethylamine N-oxide promotes atherosclerosis via CD36-dependent MAPK/JNK pathway.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro study with no human data.
PubMed 29136772 · doi:10.1016/j.biopha.2017.11.016
What was done
Apoe-/- mice fed a high-fat diet were given drinking water with or without trimethylamine N-oxide (TMAO) for 8 weeks. Histological and immunohistological analyses assessed plaque progression, macrophage recruitment, and CD36 and inflammatory cytokine expression in vivo. In vitro, mouse peritoneal elicited macrophages and RAW264.7 cells were treated with TMAO and ox-LDL, alongside CD36 siRNA knockdown or MAPK/JNK inhibitors (SB230580 and SP600125), to measure cell migration, protein expression, and foam cell formation.
What was found
The abstract reports directional findings without quantitative metrics or confidence intervals. TMAO promoted atherosclerotic plaque progression in Apoe-/- mice and increased macrophage recruitment, CD36, and proinflammatory cytokine expression in lesions. In vitro, TMAO increased macrophage migration, raised TNF-α, IL-6, and ICAM1 expression, and amplified ox-LDL-induced CD36 expression and foam cell formation. CD36 knockdown or MAPK/JNK pathway inhibition (SB230580 and SP600125) reduced the TMAO- and ox-LDL-induced increases in CD36 expression and foam cell formation.
Why it matters
This study outlines a mechanistic pathway connecting the gut microbial metabolite TMAO to foam cell formation and plaque progression via CD36 and MAPK/JNK signaling.
Limits
The abstract provides no sample sizes (n of animals or cell culture replicates) and no numerical values, effect sizes, or variance metrics. The evidence is entirely preclinical (in vitro rodent cells and transgenic mice) and may not directly translate to human cardiovascular disease.
Cited by
- supports Circulating TMAO can impact macrophages that contribute to atherosclerotic plaque formation.