Early vascular ageing in chronic kidney disease: impact of inflammation, vitamin K, senescence and genomic damage (Dai L et al.)

Authors of a review paper published recently in Nephrology Dialysis Transplantation journal discuss the link between senescence and early vascular ageing (EVA) in the context of chronic kidney disease (CKD), and they show 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.

 

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, therefore prevention and

treatment of EVA is crucial. The authors believe that in order to better develop a novel therapeutic strategy targeting EVA in patients with CKD, it is imperative to clarify the fundamental mechanisms underlying the premature ageing process and associated inflammaging. Although no direct effect of vitamin K in cellular senescence processes has been identified, it is tempting to speculate that vitamin K exerts an important role in cellular senescence given its antioxidant and anti-inflammatory effects. Apart from being an antioxidant and immune-modulator, it has been shown that vitamin K2 acts as a mitochondrial carrier, where mitochondrial dysfunction was rescued by vitamin K2 addition via restoration of adenosine triphosphate (ATP) production. The authors conclude, “Future studies testing the long-term protective effects of NRF2 and vitamin K in EVA and senescence-related endpoints are warranted and a combinative treatment with senotherapeutic agents could also be informative.”

“Vitamin K2 has been shown to be much more beneficial than vitamin K1 to support cardiovascular health. Moreover vitamin K2 was shown to have additional biological function than K1 due to different saturation of the side chain. Vitamin K2 as MK7 (MenaQ7) improved elasticity of arteries in human clinical trials and decreased inflammation in vitro,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “Inflammaging may largely contribute to pathological conditions characterized by accelerated early vascular ageing. More solid perspectives and results are to be expected from ongoing randomized clinical trials (e.g. VitaK-CAC trial,  the Aortic Valve DECalcification trial) evaluating the effect of vitamin K2 in VC progression among CKD population,” she points out.

“Based on the many clinical trials and in vitro data, we might hypothesize that vitamin K2 as MK7 might be important molecule to “fight” aging in cardiovascular system and not only,” Dr. Maresz emphasizes.

References:

Dai L, Schurgers LJ, Shiels PG, Stenvinkel P, Early vascular ageing in chronic kidney disease: impact of inflammation, vitamin K, senescence and genomic damage, Nephrology Dialysis Transplantation, Volume 35, Issue Supplement_2, March 2020, Pages ii31–ii37, https://doi.org/10.1093/ndt/gfaa006

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