One of the most recently proposed candidates as a potential trigger for cardiovascular\ndiseases is trimethylamine-N-oxide (TMAO). Possible direct effects of TMAO on myocardial\ntissue, independent of vascular damage, have been only partially explored so far. In the\npresent study, we assessed the detrimental direct effects of TMAO on cardiomyocyte contractility\nand intracellular calcium dynamics, and the ability of urolithin B-glucuronide (Uro B-gluc) in\ncounteracting TMAO-induced cell damage. Cell mechanics and calcium transients were measured,\nand ultrastructural analysis was performed in ventricular cardiomyocytes isolated from the heart\nof normal adult rats. Cells were either untreated, exposed to TMAO, or to TMAO and Uro\nB-gluc. TMAO exposure worsened cardiomyocyte mechanics and intracellular calcium handling,\nas documented by the decrease in the fraction of shortening (FS) and the maximal rate of\nshortening and re-lengthening, associated with reduced efficiency in the intracellular calcium removal.\nUltrastructurally, TMAO-treated cardiomyocytes also exhibited glycogen accumulation, a higher\nnumber of mitochondria and lipofuscin-like pigment deposition, suggesting an altered cellular\nenergetic metabolism and a higher rate of protein oxidative damage, respectively. Uro B-gluc led\nto a complete recovery of cellular contractility and calcium dynamics, and morphologically to\na reduced glycogen accumulation. We demonstrated for the first time a direct negative role of\nTMAO on cardiomyocyte functional properties and the ability of Uro B-gluc in counteracting these\ndetrimental effects.
Loading....