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Molecules 2018, 23(3), 549;

Trimethylamine-N-Oxide (TMAO)-Induced Impairment of Cardiomyocyte Function and the Protective Role of Urolithin B-Glucuronide

Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy
Department of Veterinary Science, University of Parma, Strada del Taglio 10, 43126 Parma, Italy
Department of Medicine and Surgery, University of Parma, Via A. Gramsci 14, 43126 Parma, Italy
Department of Food and Drugs, University of Parma, Parco Area delle Scienze 27/A, 43124 Parma, Italy
Department of Nutrition, University of California, 3143 Meyer Hall One Shields Avenue, Davis, CA 95616-5270, USA
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Received: 24 January 2018 / Revised: 21 February 2018 / Accepted: 26 February 2018 / Published: 1 March 2018
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One of the most recently proposed candidates as a potential trigger for cardiovascular diseases is trimethylamine-N-oxide (TMAO). Possible direct effects of TMAO on myocardial tissue, independent of vascular damage, have been only partially explored so far. In the present study, we assessed the detrimental direct effects of TMAO on cardiomyocyte contractility and intracellular calcium dynamics, and the ability of urolithin B-glucuronide (Uro B-gluc) in counteracting TMAO-induced cell damage. Cell mechanics and calcium transients were measured, and ultrastructural analysis was performed in ventricular cardiomyocytes isolated from the heart of normal adult rats. Cells were either untreated, exposed to TMAO, or to TMAO and Uro B-gluc. TMAO exposure worsened cardiomyocyte mechanics and intracellular calcium handling, as documented by the decrease in the fraction of shortening (FS) and the maximal rate of shortening and re-lengthening, associated with reduced efficiency in the intracellular calcium removal. Ultrastructurally, TMAO-treated cardiomyocytes also exhibited glycogen accumulation, a higher number of mitochondria and lipofuscin-like pigment deposition, suggesting an altered cellular energetic metabolism and a higher rate of protein oxidative damage, respectively. Uro B-gluc led to a complete recovery of cellular contractility and calcium dynamics, and morphologically to a reduced glycogen accumulation. We demonstrated for the first time a direct negative role of TMAO on cardiomyocyte functional properties and the ability of Uro B-gluc in counteracting these detrimental effects. View Full-Text
Keywords: ellagitannins; cardiomyocyte mechanics; cardiovascular diseases; Trimethylamine-N-oxide; urolithins ellagitannins; cardiomyocyte mechanics; cardiovascular diseases; Trimethylamine-N-oxide; urolithins

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Savi, M.; Bocchi, L.; Bresciani, L.; Falco, A.; Quaini, F.; Mena, P.; Brighenti, F.; Crozier, A.; Stilli, D.; Del Rio, D. Trimethylamine-N-Oxide (TMAO)-Induced Impairment of Cardiomyocyte Function and the Protective Role of Urolithin B-Glucuronide. Molecules 2018, 23, 549.

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