Objectives:
ESR12 aims to develop high affinity peptides for apoptotic remnants based on fetuin-A theranostics targeting tissue microcalcifications and colloidal calcifying mineral-protein complexes, CPPs (fetuin-A, annexin A5) as imaging agents and theranostics. Using in house preclinical models to address CPPs, apoptosis and calcification we will test these imaging agents and theranostics. Additionally, we will build a miniaturised cell-based platform covering multiple cardiovascular key functions (such as calcification, fibrosis and inflammation).
Methodologies:
1. Validate imaging agents (Fetuin-A) in vivo for apoptosis (apoE:sm22ahDTr mice in collaboration with ESR3) and calcification (fetuin-A deficient DBA/2 mice, warfarin mouse model). This will include nutraceutical/dietary and pharmaceutical intervention (magnesium, phosphate, vitamin K and oral anticoagulants) as well as treatments suggested by results from ESR2, 3, 5, and 7 as they become available.
2. Validation of Fetuin-A as theranostic agent in animal models to evaluate vascular apoptosis and calcification in relation to plaque stability. This will provide ESR2, ESR3, ESR5 and ESR6 with fetuin-A based theranostics.
3. Utilising a miniaturised cell-based platform to analyse differences in proliferation, migration and invasion (xCELLigence®) and cell functions by multiplex fluorescence analyses using cell-function-reporters (Fetuin-A). Integrate available miniaturised assays for several major “cardiovascular” functions in the main cellular culprits in vascular inflammation, fibrosis, and calcification; endothelium, macrophages and vascular smooth muscle cells.
