Key result
Cardiovascular patients had two-fold higher plasma TMA compared to healthy humans, and TMA, but not TMAO, reduced cardiomyocyte viability and degraded protein structures in vitro.
Why the study?
Data on TMAO in cardiovascular disease are contradictory with obscure mechanisms, and the cardiovascular role of its precursor TMA has not drawn attention.
Does TMA or TMAO exert direct cytotoxic effects and correlate with cardiovascular disease?
Observational
Does TMA or TMAO exert direct cytotoxic effects and correlate with cardiovascular disease?
TMA, rather than TMAO, may be the actual uremic toxin and marker of cardiovascular risk, as it exerts direct cytotoxic effects on cardiomyocytes and degrades proteins.
Answers are grounded in this paper and cite their sources.
TMA may be a direct cardiomyocyte toxin distinct from TMAO; leaves open its role as a modifiable cardiovascular risk marker.
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.
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Jaworska et al. (2019) conducted an observational in Cardiovascular disease requiring aortic valve replacement. Cardiovascular disease (qualified for aortic valve replacement) vs. Healthy humans was evaluated on Plasma TMA levels (two-fold higher, p=<0.001). Cardiovascular patients had two-fold higher plasma TMA compared to healthy humans, and TMA, but not TMAO, reduced cardiomyocyte viability and degraded protein structures in vitro.
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