Targeting proinflammatory cytokines ameliorates calcifying phenotype conversion of vascular progenitors under uremic conditions in vitro

Bjoern Hegner*, Theres Schaub, Daniel Janke, Daniel Zickler, Claudia Lange, Matthias Girndt, Joachim Jankowski, Ralf Schindler, Duska Dragun

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

10 Citations (Web of Science)

Abstract

Severe vascular calcification develops almost invariably in chronic kidney patients posing a substantial risk to quality of life and survival. This unmet medical need demands identification of novel therapeutic modalities. We aimed to pinpoint components of the uremic microenvironment triggering differentiation of vascular progenitors to calcifying osteoblast-like cells. In an unbiased approach, assessing the individual potency of 63 uremic retention solutes to enhance calcific phenotype conversion of vascular progenitor cells, the pro-inflammatory cytokines IL-1 beta and TNF-alpha were identified as the strongest inducers followed by FGF-2, and PTH. Pharmacologic targeting of these molecules alone or in combination additively antagonized pro-calcifying properties of sera from uremic patients. Our findings stress the importance of pro-inflammatory cytokines above other characteristic components of the uremic microenvironment as key mediators of calcifying osteoblastic differentiation in vascular progenitors. Belonging to the group of "middle-sized molecules", they are neither effectively removed by conventional dialysis nor influenced by established supportive therapies. Specific pharmacologic interventions or novel extracorporeal approaches may help preserve regenerative capacity and control vascular calcification due to uremic environment.
Original languageEnglish
Article number12087
Number of pages11
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 14 Aug 2018

Keywords

  • MESENCHYMAL STEM-CELLS
  • CHRONIC KIDNEY-DISEASE
  • HIGH CUTOFF HEMOFILTRATION
  • ARTERIAL CALCIFICATION
  • HEMODIALYSIS-PATIENTS
  • STROMAL CELLS
  • HUMAN PLASMA
  • INTERLEUKIN-1
  • TOXINS
  • VARIABILITY

Cite this