Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 02-106 Warsaw, Poland.
Department of Hypertension and Diabetology, Medical University of Gdansk, 80-211 Gdansk, Poland.
Toxins (Basel). 2019 Aug 26;11(9):490. doi: 10.3390/toxins11090490.
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 ( < 0.001) and a trend towards higher plasma TMAO ( = 0.07). In CP plasma, TMA was inversely correlated with an estimated glomerular filtration rate (eGFR, = 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.
三甲胺氮氧化物（TMAO）被认为是心血管疾病的标志物和介质。然而，数据存在矛盾，其机制尚不清楚。令人惊讶的是，即使几十年前就提出了 TMA 的毒性作用，但 TMAO 前体三甲胺（TMA）在心血管研究中并未引起关注。我们评估了健康人类（HH）和符合主动脉瓣置换术（CP）条件的心血管患者的血浆 TMA 和 TMAO 水平。使用 MTT 试验评估 TMA 和 TMAO 在大鼠心肌细胞中的细胞毒性。使用荧光相关光谱法评估 TMA 和 TMAO 对白蛋白和乳酸脱氢酶（LDH）的影响。与 HH 相比，CP 的血浆 TMA 高两倍（<0.001），血浆 TMAO 呈升高趋势（=0.07）。在 CP 血浆中，TMA 与估算肾小球滤过率（eGFR，=0.002）呈负相关。TMA 但不是 TMAO 降低了心肌细胞活力。与 TMA 孵育而不是 TMAO 孵育导致 LDH 和白蛋白的蛋白质结构降解。总之，CP 显示出增加的血浆 TMA，其与 eGFR 呈负相关。TMA 但不是 TMAO 对心肌细胞产生负面影响，可能是因为其对蛋白质的干扰作用。因此，TMA 可能是一种毒素和心血管风险的标志物。
