Project Details
Projekt
Chronic uremic "inflammaging": activation of pattern recognition receptors via DAMP/alarmines in vascular smooth-muscle cells
Subject Area
Nephrology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 510095677
Chronic uremic inflammation is the cause of a premature onset of severe uremic vascular pathology, which accounts for a significant proportion of the greatly increased mortality of patients with chronic kidney disease (CKD) and is comparable to that of aging. The associated medial vascular calcification causes an increase in vascular stiffness with associated significant rheological changes. Targeted therapeutic concepts that reduce the associated cardiovascular mortality of CKD patients are missing so far. Our project aims to investigate: 1) Identification of central pathophysiological pathways and key therapeutic targets in the context of PRR mediated uremic "inflammaging" and uremic vascular progeria. Establishment of novel therapeutic options related to uremic "inflammaging" and uremic vascular progeria and their testing in in vitro / ex vivo / in vivo systems. Extensive preliminary investigations of our working group provide indications of interesting targets here, which will be investigated in detail within the framework of the project. These targets include the "pattern recognition" receptors (Toll-like receptors (TLR) and inflammasomes) as components of the innate immune system and the IL-1 cytokine family associated with them. A better understanding of these central mechanisms will lay the basis for the development of new, effective therapeutic concepts. 2) Transferability to the human system: identification of uremic alterations in the transcriptome of human vessels of uremic patients. 3) Detection of potential biomarkers for diagnosis and severity assessment of uremic "inflammaging" and uremic vascular progeria in the cohort of "CURE CKD-inflammation", "CURE HD-inflammation" and "BIS study". Association of biomarkers with cardiovascular mortality and morbidity in the "BIS" cohort. A broad spectrum of established histological, molecular and cell biological methods will be used to describe inflammation-related phenotype change of vascular smooth muscle cells and the associated uremic-vascular pathology. In particular, our most recently established methods will be applied. The symbiosis of clinical and basic scientific expertise of both applicants in the research field offers best conditions for a successful project implementation.
DFG Programme
Research Grants
