TMA, A Forgotten Uremic Toxin, but Not TMAO, Is Involved in Cardiovascular Pathology.
Trimethylamine-N-oxide (TMAO) has been suggested as a marker and mediator of cardiovascular diseases. However, data are contradictory, and the mechanisms are obscure. Strikingly, the role of the TMAO precursor trimethylamine (TMA) has not drawn attention in cardiovascular studies even though toxic effects of TMA were proposed several decades ago. We assessed plasma TMA and TMAO levels in healthy humans (HH) and cardiovascular patients qualified for aortic valve replacement (CP). The cytotoxicity of TMA and TMAO in rat cardiomyocytes was evaluated using an MTT test. The effects of TMA and TMAO on albumin and lactate dehydrogenase (LDH) were assessed using fluorescence correlation spectroscopy. In comparison to HH, CP had a two-fold higher plasma TMA (p < 0.001) and a trend towards higher plasma TMAO (p = 0.07). In CP plasma, TMA was inversely correlated with an estimated glomerular filtration rate (eGFR, p = 0.002). TMA but not TMAO reduced cardiomyocytes viability. Incubation with TMA but not TMAO resulted in the degradation of the protein structure of LDH and albumin. In conclusion, CP show increased plasma TMA, which is inversely correlated with eGFR. TMA but not TMAO exerts negative effects on cardiomyocytes, likely due to its disturbing effect on proteins. Therefore, TMA but not TMAO may be a toxin and a marker of cardiovascular risk.
['Jaworska|Kinga|K|0000-0002-0281-015X', 'Hering|Dagmara|D|0000-0003-4649-9524', 'Mosieniak|Grażyna|G|', 'Bielak-Zmijewska|Anna|A|', 'Pilz|Marta|M|0000-0002-7519-2532', 'Konwerski|Michał|M|', 'Gasecka|Aleksandra|A|', 'Kapłon-Cieślicka|Agnieszka|A|', 'Filipiak|Krzysztof|K|', 'Sikora|Ewa|E|0000-0002-1111-1748', 'Hołyst|Robert|R|', 'Ufnal|Marcin|M|0000-0003-0088-8284']
D000328:Adult D000368:Aged D000818:Animals D015415:Biomarkers D002318:Cardiovascular Diseases D016022:Case-Control Studies D002470:Cell Survival D002478:Cells, Cultured D005260:Female D005919:Glomerular Filtration Rate D064368:Healthy Volunteers D006801:Humans D008297:Male D008744:Methylamines D032383:Myocytes, Cardiac D051381:Rats
TMAO trimethylamine bacterial metabolites biomarkers