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.

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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