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Trimethylamine-N-Oxide (TMAO)-Induced Impairment of Cardiomyocyte Function and the Protective Role of Urolithin B-Glucuronide
- Source :
- Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry, Molecules, Vol 23, Iss 3, p 549 (2018), Molecules; Volume 23; Issue 3; Pages: 549
- Publication Year :
- 2018
- Publisher :
- MDPI AG, 2018.
-
Abstract
- 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.
- Subjects :
- Male
0301 basic medicine
Cardiotonic Agents
Pharmaceutical Science
chemistry.chemical_element
Trimethylamine N-oxide
ellagitannins
cardiomyocyte mechanics
cardiovascular diseases
Trimethylamine-N-oxide
urolithins
030204 cardiovascular system & hematology
Calcium
Article
Mitochondria, Heart
Calcium in biology
Analytical Chemistry
lcsh:QD241-441
Contractility
Methylamines
03 medical and health sciences
chemistry.chemical_compound
Glucuronides
0302 clinical medicine
lcsh:Organic chemistry
Coumarins
Drug Discovery
medicine
Animals
Myocytes, Cardiac
Calcium Signaling
Physical and Theoretical Chemistry
Cell damage
Calcium signaling
Glycogen
Chemistry
Organic Chemistry
medicine.disease
Urolithin B
Rats
Cell biology
030104 developmental biology
Chemistry (miscellaneous)
Molecular Medicine
Subjects
Details
- ISSN :
- 14203049
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....003b03b0f72c377026c6a8f89694486f