Trimethylamine But Not Trimethylamine Oxide Increases With Age in Rat Plasma and Affects Smooth Muscle Cells
Kinga Jaworska1, Marek Konop1, Tomasz Hutsch1
1Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw, Poland.
Abstract:
It has been suggested that trimethylamine oxide (TMAO), a liver oxygenation product of gut bacteria-produced trimethylamine (TMA), is a marker of cardiovascular risk. However, mechanisms of the increase and biological effects of TMAO are obscure. Furthermore, the potential role of TMAO precursor, that is TMA, has not been investigated. We evaluated the effect of age, a cardiovascular risk factor, on plasma levels of TMA and TMAO, gut bacteria composition, gut-to-blood penetration of TMA, histological and hemodynamic parameters in 3-month-old and 18-month-old, male, Sprague-Dawley and Wistar-Kyoto rats. Cytotoxicity of TMA and TMAO was studied in human vascular smooth muscle cells. Older rats showed significantly different gut bacteria composition, a significantly higher gut-to-blood TMA penetration, and morphological and hemodynamic alterations in intestines. In vitro, TMA at concentration of 500 µmol/L (2-fold higher than in portal blood) decreased human vascular smooth muscle cells viability. In contrast, TMAO at 1,000-fold higher concentration than physiological one had no effect on human vascular smooth muscle cells viability. In conclusion, older rats show higher plasma level of TMA due to a "leaky gut". TMA but not TMAO affects human vascular smooth muscle cells viability. We propose that TMA but not TMAO may be a marker and mediator of cardiovascular risk.
Insights
Older rats exhibit increased trimethylamine (TMA) due to a "leaky gut," potentially increasing cardiovascular risk. TMA, unlike trimethylamine oxide (TMAO), directly impacts vascular cell viability, suggesting TMA as a key risk factor.
Area of Science:
- Microbiology
- Cardiovascular Science
- Gastroenterology
Background:
- Trimethylamine oxide (TMAO) is a proposed cardiovascular risk marker.
- Mechanisms and biological effects of TMAO remain unclear.
- The role of TMAO precursor, trimethylamine (TMA), is understudied.
Purpose of the Study:
- To investigate the effect of age on TMA and TMAO plasma levels.
- To analyze gut bacteria composition and TMA gut-to-blood penetration in aging rats.
- To assess the cytotoxicity of TMA and TMAO on human vascular smooth muscle cells.
Main Methods:
- Comparison of 3-month-old and 18-month-old Sprague-Dawley and Wistar-Kyoto rats.
- Analysis of plasma TMA/TMAO levels, gut microbiota, and intestinal parameters.
- In vitro cytotoxicity assays using human vascular smooth muscle cells.
Main Results:
- Older rats displayed altered gut bacteria and increased TMA gut-to-blood penetration.
- TMA, at concentrations found in portal blood, reduced vascular smooth muscle cell viability.
- TMAO showed no cytotoxicity even at significantly higher concentrations.
Conclusions:
- Aging increases plasma TMA levels, linked to a
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