Trimethylamine N-oxide in atherogenesis: impairing endothelial self-repair capacity and enhancing monocyte adhesion

Biosci Rep. 2017 Mar 2;37(2):BSR20160244. doi: 10.1042/BSR20160244. Print 2017 Apr 30.

Abstract

Several studies have reported a strong association between high plasma level of trimethylamine N-oxide (TMAO) and atherosclerosis development. However, the exact mechanism underlying this correlation is unknown. In the present study, we try to explore the impact of TMAO on endothelial dysfunction. After TMAO treatment, human umbilical vein endothelial cells (HUVECs) showed significant impairment in cellular proliferation and HUVECs-extracellular matrix (ECM) adhesion compared with control. Likewise, TMAO markedly suppressed HUVECs migration in transwell migration assay and wound healing assay. In addition, we found TMAO up-regulated vascular cell adhesion molecule-1 (VCAM-1) expression, promoted monocyte adherence, activated protein kinase C (PKC) and p-NF-κB. Interestingly, TMAO-stimulated VCAM-1 expression and monocyte adherence were diminished by PKC inhibitor. These results demonstrate that TMAO promotes early pathological process of atherosclerosis by accelerating endothelial dysfunction, including decreasing endothelial self-repair and increasing monocyte adhesion. Furthermore, TMAO-induced monocyte adhesion is partly attributable to activation of PKC/NF-κB/VCAM-1.

Keywords: Atherosclerosis; Endothelial dysfunction; PKC/ NF-κB; TMAO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / blood*
  • Atherosclerosis / etiology*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Cell Adhesion / physiology*
  • Cells, Cultured
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Methylamines / blood*
  • Monocytes / metabolism*
  • Monocytes / pathology
  • NF-kappa B / metabolism
  • Protein Kinase C / metabolism
  • Signal Transduction / physiology
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Methylamines
  • NF-kappa B
  • Vascular Cell Adhesion Molecule-1
  • Protein Kinase C
  • trimethyloxamine