Remnant-like particles accelerate endothelial progenitor cells senescence and induce cellular dysfunction via an oxidative mechanism

Atherosclerosis. 2009 Feb;202(2):405-14. doi: 10.1016/j.atherosclerosis.2008.05.024. Epub 2008 May 22.

Abstract

Remnant-like particles (RLPs) are closely associated with coronary heart disease and can induce endothelial dysfunction through oxidative mechanisms. Many risk factors accelerate the onset of endothelial progenitor cells (EPCs) senescence via increased oxidative stress. In this study, we investigated the effect of RLPs on EPCs senescence and function. RLPs were isolated from postprandial plasma of hypertriglyceridemic patients by use of the immunoaffinity gel mixture of anti-apoA-1 and anti-apoB-100 monoclonal antibodies. Our results show that EPCs became senescent as determined by senescence-associated acidic beta-galactosidase (SA-beta-Gal) staining after ex vivo cultivation without any stimulation. Co-incubation with RLPs accelerated the increase in SA-beta-Gal-positive EPCs. The acceleration of RLPs-induced EPCs senescence occurred dose-dependently with a maximal effect when EPCs were treated with RLPs at 0.10 mg cholesterol/mL (P<0.01). Moreover, RLPs decreased adhesion, migration and proliferation capacities of EPCs as assessed by adherence to fibronectin, modified Boyden chamber technique and MTT assay (P<0.01), respectively. RLPs increased nitrotyrosine staining in EPCs. However, RLPs-induced EPCs senescence and dysfunction were significantly inhibited by pre-treatment of superoxide dismutase (50 U/mL) (P<0.05). Our results provide evidence that RLPs accelerate the onset of EPC senescence via increased oxidative stress, accompanying with the impairment of adhesion, migration and proliferation capacities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology
  • Cell Division / drug effects
  • Cell Division / physiology
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cellular Senescence / drug effects
  • Cellular Senescence / physiology
  • Cholesterol / pharmacology*
  • Endothelium, Vascular / cytology*
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Lipoproteins / pharmacology*
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Peroxynitrous Acid / metabolism
  • Superoxide Dismutase / metabolism
  • Triglycerides / pharmacology*

Substances

  • Lipoproteins
  • Triglycerides
  • remnant-like particle cholesterol
  • Peroxynitrous Acid
  • Cholesterol
  • Superoxide Dismutase