title: Oxidized low-density lipoproteins enhance expression and activity of CD39 and CD73 in the human aortic valve endothelium.
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.
authors.affiliation: a Department of Biochemistry , Medical University of Gdansk , Gdansk , Poland.|b Heart Science Centre , Imperial College London at Harefield Hospital , Harefield , UK.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kaniewska-Bednarczuk
authors.affiliation: c Department of Life Sciences , Imperial College London , London, UK.
authors.forename: Michał
authors.initials: M
authors.lastname: Mielcarek
authors.affiliation: b Heart Science Centre , Imperial College London at Harefield Hospital , Harefield , UK.
authors.forename: Adrian H
authors.initials: AH
authors.lastname: Chester
authors.affiliation: a Department of Biochemistry , Medical University of Gdansk , Gdansk , Poland.
authors.forename: Ewa M
authors.initials: EM
authors.lastname: Slominska
authors.affiliation: b Heart Science Centre , Imperial College London at Harefield Hospital , Harefield , UK.
authors.forename: Magdi H
authors.initials: MH
authors.lastname: Yacoub
authors.affiliation: a Department of Biochemistry , Medical University of Gdansk , Gdansk , Poland.
authors.forename: Ryszard T
authors.initials: RT
authors.lastname: Smolenski
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D001021:Aortic Valve / Q000378:metabolism* / Q000473:pathology; D001081:Apyrase / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006349:Heart Valve Diseases / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D001081:Apyrase; C067869:CD39 antigen
keywords: CD39; CD73; Ox-LDL; aortic valve; endothelium