Neutrophil-dependent pentraxin-3 and reactive oxygen species production modulate endothelial dysfunction in haemodialysis patients

Giuseppe Grandaliano, Maria Pia Dell'Oglio, Simona Simone, Marco Ciccone, Roberto Corciulo, Michele Gesualdo, Annapaola Zito, Francesca Cortese, Giuseppe Castellano, Margherita Gigante, Loreto Gesualdo, Giovanni Battista Pertosa

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12 Citazioni (Scopus)

Abstract

Background. The aim of this study was to investigate neutrophil activation and its role in long pentraxin-3 (PTX3) release and oxidative stress generation during haemodialysis (HD) and to correlate neutrophil PTX3 and oxidant expression with endothelial dysfunction. Methods. Forty-seven uraemic patients on stable HD, 12 healthy subjects and 15 patients with congestive heart failure (New York Heart Association classes III and IV) were enrolled. Neutrophil PTX3 protein expression was evaluated by confocal microscopy. L-selectin expression, intracellular PTX3 localization and reactive oxygen species (ROS) generation in human neutrophils were measured by flow cytometry. NADPHdependent superoxide generation was investigated by chemiluminescence. PTX3 plasma concentrations were measured by ELISA. Endothelial dysfunction was studied by flow-mediated dilation (FMD). Results. The low baseline levels of FMD significantly improved after HD, but worsened by 24 h. A significant up-regulation of PTX3 protein expression, localized within secondary granules, was detected in neutrophils isolated at 30 and 240 min of HD, along with an increase in L-selectin expression. The upregulation in intracellular PTX3 in neutrophils was associated with a significant increase in PTX3 plasma concentrations at 240 min. HD increased ROS production and NADPH oxidase activity in neutrophils. In a univariate analysis, pre-treatment with FMD was inversely correlated with PTX3 expression and ROS generation in neutrophils. In a multivariate analysis, both circulating pre-HD PTX3 and intracellular ROS generation by neutrophils were independent predictors of abnormal FMD. Conclusions. Neutrophil overexpression of PTX3 is associated with ROS overproduction and endothelial dysfunction and may represent an emerging marker of vascular damage progression in HD patients.
Lingua originaleEnglish
pagine (da-a)1540-1549
Numero di pagine10
RivistaNephrology Dialysis Transplantation
Volume32
DOI
Stato di pubblicazionePubblicato - 2017

Keywords

  • Biomarkers
  • C-Reactive Protein
  • Endothelial dysfunction
  • Endothelium, Vascular
  • Female
  • Haemodialysis
  • Humans
  • Male
  • Middle Aged
  • Neutrophil Activation
  • Neutrophils
  • Oxidative Stress
  • Oxidative stress
  • Pentraxin-3
  • Reactive Oxygen Species
  • Renal Dialysis
  • Serum Amyloid P-Component
  • Up-Regulation
  • Vascular Diseases

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