The Impact of Semicarbazide Sensitive Amine Oxidase Activity on Rat Aortic Vascular Smooth Muscle Cells

Vesna Manasieva, Shori Thakur, Lisa A. Lione, Anwar R. Baydoun, John Skamarauskas, Jason M. Karch (Editor), Joseph W. Gordon (Editor)

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Abstract

Semicarbazide-sensitive amine oxidase (SSAO) is both a soluble- and membrane-bound transmembrane protein expressed in the vascular endothelial and in smooth muscle cells. In vascular endothelial cells, SSAO contributes to the development of atherosclerosis by mediating a leukocyte adhesion cascade; however, its contributory role in the development of atherosclerosis in VSMCs has not yet been fully explored. This study investigates SSAO enzymatic activity in VSMCs using methylamine and aminoacetone as model substrates. The study also addresses the mechanism by which SSAO catalytic activity causes vascular damage, and further evaluates the contribution of SSAO in oxidative stress formation in the vascular wall. SSAO demonstrated higher affinity for aminoacetone when compared to methylamine (Km = 12.08 µM vs. 65.35 µM). Aminoacetone- and methylamine-induced VSMCs death at concentrations of 50 & 1000 µM, and their cytotoxic effect, was reversed with 100 µM of the irreversible SSAO inhibitor MDL72527, which completely abolished cell death. Cytotoxic effects were also observed after 24 h of exposure to formaldehyde, methylglyoxal and H 2O 2. Enhanced cytotoxicity was detected after the simultaneous addition of formaldehyde and H 2O 2, as well as methylglyoxal and H 2O 2. The highest ROS production was observed in aminoacetone- and benzylamine-treated cells. MDL72527 abolished ROS in benzylamine-, methylamine- and aminoacetone-treated cells (**** p < 0.0001), while βAPN demonstrated inhibitory potential only in benzylamine-treated cells (* p < 0.05). Treatment with benzylamine, methylamine and aminoacetone reduced the total GSH levels (**** p < 0.0001); the addition of MDL72527 and βAPN failed to reverse this effect. Overall, a cytotoxic consequence of SSAO catalytic activity was observed in cultured VSMCs where SSAO was identified as a key mediator in ROS formation. These findings could potentially associate SSAO activity with the early developing stages of atherosclerosis through oxidative stress formation and vascular damage.

Original languageEnglish
Article number4946
Pages (from-to)1-19
Number of pages19
JournalInternational Journal of Molecular Sciences (IJMS)
Volume24
Issue number5
Early online date3 Mar 2023
DOIs
Publication statusPublished - 3 Mar 2023

Keywords

  • Article
  • vascular smooth muscle cells
  • semicarbazide-sensitive amine oxidase
  • methylamine
  • aminoacetone
  • formaldehyde
  • methylglyoxal
  • hydrogen peroxide
  • reactive oxygen species
  • Hydrogen Peroxide/pharmacology
  • Reactive Oxygen Species/pharmacology
  • Rats
  • Formaldehyde/pharmacology
  • Muscle, Smooth, Vascular/metabolism
  • Benzylamines/pharmacology
  • Animals
  • Endothelial Cells/metabolism
  • Methylamines/metabolism
  • Amine Oxidase (Copper-Containing)/metabolism
  • Pyruvaldehyde/pharmacology

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