Molecular Profiling and Novel Treatment Strategies of Vascular Ageing in Chronic Kidney Disease

Cardiovascular disease due to early vascular ageing (EVA) is the leading global cause of premature death. We find a major discrepancy between chronological and biological vascular age in chronic kidney disease (CKD).

Whereas established risk factors cannot explain the rapid vascular ageing process in CKD, our results suggest that the toxic uremic milieu drives accumulation of hyperfunctional senescent cells that mediate vascular dysfunction via secretion of inflammatory mediators, repressed activity of the cytoprotective factor Nrf2, gut dysbiosis and somatic mutations that promote EVA.We use longitudinal data and cutting-edge molecular profiling technologies on samples from large, unique biobanks with vascular biopsies from a large number of patients with extreme EVA.

The group has all the tools necessary to do molecular profiling of EVA and identify novel targets for interventions, including cellular analysis and advanced DNA/RNA analysis.

Specifically, we assess the combination of functional and structural vascular properties in relation to scRNA sequencing, transcriptomics and prevalence of “killer clones”.

A main hypothesis of the project is that nutritional senotherapeutic combinations and/or Nrf2 agonists have beneficial effects on vascular functions ex vivo.

We aim to identify individuals at risk for EVA and introduce novel interventions that could limit the gap between “health span” and “life span” thus rapidly being able to implement findings in clinical practice.