TMA, beyond TMAO, might contribute to vascular inflammation by disturbing mitochondrial functions in macrophages.

Emerging evidence highlights conflicting data regarding the roles of trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) plasma levels in cardiovascular diseases. In this study, we investigate in THP-1 monocytes the pro-inflammatory effects of TMA and TMAO at both physiological and pathological concentrations previously measured in a human cohort, focusing on their impact on ATP production, mitochondrial gene expression, mitochondrial membrane potential (ΔΨm), and mitochondrial DNA copy number (mtDNAcn). Results show that 0.6 μM and 1.2 μM TMA as well as 40 μM TMAO increase the expression levels of the pro-inflammatory IL-8, while the anti-inflammatory cytokine IL-10 was upregulated by 1.2 μM TMA and 40 μM TMAO. An increase in the expression levels of mitochondrial genes MT-ATP6, MT-CO1, MT-CYB and MT-ND6 was measured on all conditions tested, while no significant changes in mtDNAcn were observed. Remarkably, TMA (0.6 μM and 1.2 μM), but not TMAO, decreases ATP content and increases the mitochondrial membrane potential in THP-1 cells after 24 h of incubation. In conclusion, our study suggests that not only circulating TMAO but also TMA may contribute to vascular inflammation by disturbing mitochondrial functions in monocytes. This evidence underscores the need for further investigations to better understand the effects of these metabolites on cardiovascular health.