Metformin regulates oxLDL-facilitated endothelial dysfunction by modulation of SIRT1 through repressing LOX-1-modulated oxidative signaling

Oncotarget. 2016 Mar 8;7(10):10773-87. doi: 10.18632/oncotarget.7387.

Abstract

It is suggested that oxLDL is decisive in the initiation and development of atherosclerotic injuries. The up-regulation of oxidative stress and the generation of ROS act as key modulators in developing pro-atherosclerotic and anti-atherosclerotic processes in the human endothelial wall. In this present study, we confirmed that metformin enhanced SIRT1 and AMPK expression in human umbilical vein endothelial cells (HUVECs). Metformin also inhibited oxLDL-increased LOX-1 expression and oxLDL-collapsed AKT/eNOS levels. However, silencing SIRT1 and AMPK diminished the protective function of metformin against oxidative injuries. These results provide a new insight regarding the possible molecular mechanisms of metformin.

Keywords: Gerotarget; SIRT1; endothelial dysfunction; metformin; oxLDL.

MeSH terms

  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lipoproteins, LDL / metabolism*
  • Metformin / pharmacology*
  • Oxidation-Reduction
  • Oxidative Stress / drug effects*
  • Scavenger Receptors, Class E / metabolism*
  • Signal Transduction
  • Sirtuin 1 / metabolism*
  • Up-Regulation

Substances

  • Lipoproteins, LDL
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • oxidized low density lipoprotein
  • Metformin
  • SIRT1 protein, human
  • Sirtuin 1