Early vascular ageing in chronic kidney disease: impact of inflammation, vitamin K, senescence and genomic damage

Lu Dai, Leon J. Schurgers, Paul G. Shiels, Peter Stenvinkel*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

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Abstract

Chronic kidney disease (CKD) is a clinical model of premature ageing characterized by cardiovascular disease, persistent uraemic inflammation, osteoporosis muscle wasting and frailty. The accelerated early vascular ageing (EVA) process mediated by medial vascular calcification (VC) is a hallmark of senescence as well as a strong predictor of cardiovascular morbidity and mortality in the CKD population. Current clinical therapeutic strategies and novel treatments for VC have not yet been proven to prevent or reverse VC progression in patients with CKD. Knowledge of the fundamental mechanism underlying EVA is urgently needed to identify and develop novel and efficient therapeutic targets for VC and EVA. An accumulating body of evidence indicates that deoxyribonucleic acid (DNA) damage-induced cellular senescence and 'inflammaging' may largely contribute to such pathological conditions characterized by accelerated EVA. Growing evidence shows that nuclear factor erythroid 2-related factor 2 (NRF2) signalling and vitamin K play a crucial role in counteracting oxidative stress, DNA damage, senescence and inflammaging, whereby NRF2 activation and vitamin K supplementation may provide a novel treatment target for EVA. In this review we discuss the link between senescence and EVA in the context of CKD, with a focus on the role of NRF2 and vitamin K in DNA damage signalling, senescence and inflammaging.

Original languageEnglish
Pages (from-to)II31-II37
Number of pages7
JournalNephrology Dialysis Transplantation
Volume35
DOIs
Publication statusPublished - Mar 2020

Keywords

  • age
  • cardiovascular
  • CKD
  • inflammation
  • oxidative stress
  • OXIDATIVE STRESS
  • DNA-DAMAGE
  • CELLULAR SENESCENCE
  • KAPPA-B
  • CALCIFICATION
  • NRF2
  • ACTIVATION
  • PATHWAY
  • SUPPLEMENTATION
  • MECHANISMS

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