Oxidized low-density lipoproteins enhance expression and activity of CD39 and CD73 in the human aortic valve endothelium

Nucleosides Nucleotides Nucleic Acids. 2016 Dec;35(10-12):713-719. doi: 10.1080/15257770.2016.1163377.

Abstract

Extracellular nucleotides regulate thrombosis, inflammation, and immune response. Ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and ecto-5'-nucleotidase (CD73) convert extracellular nucleotides in a sequential order: ATP to ADP, AMP, and then to adenosine. In this study, we aimed to test an effect of oxidized low-density lipoprotein (ox-LDL) on CD39 and CD73 in endothelial cells. Human aortic valve endothelial cells were exposed to ox-LDL for 24-48 h. Next, the activity, protein expression, and mRNA transcripts level of CD39 and CD73 were characterized by an incubation with ATP or AMP followed by high-performance liquid chromatography analysis of media as well as western blots and qPCR. CD73 activity in human valve endothelial cells was increased in presence of ox-LDL (4.04 ± 0.32 nmol/mg prot./min, mean +/- SEM) as compared with control (2.75 ± 0.21 nmol/mg prot/min). There was almost no effect of ox-LDL on CD39 activity. A similar effect was observed for mRNA and protein expression. In conclusion, we found that ox-LDL modulated CD39 and CD73 activity in the endothelium, which may contribute to relevant pathologies and featured treatments.

Keywords: CD39; CD73; Ox-LDL; aortic valve; endothelium.

MeSH terms

  • 5'-Nucleotidase / genetics
  • 5'-Nucleotidase / metabolism*
  • Adult
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Aortic Valve / metabolism*
  • Aortic Valve / pathology
  • Apyrase / genetics
  • Apyrase / metabolism*
  • Cells, Cultured
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Female
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Gene Expression
  • Heart Valve Diseases / metabolism*
  • Humans
  • Lipoproteins, LDL / physiology*
  • Male
  • Middle Aged
  • Primary Cell Culture
  • Young Adult

Substances

  • Antigens, CD
  • GPI-Linked Proteins
  • Lipoproteins, LDL
  • oxidized low density lipoprotein
  • 5'-Nucleotidase
  • NT5E protein, human
  • Apyrase
  • CD39 antigen