A03-The innate immune sensors RIG-I and MDA5 in aortic inflammation and calcification

In this project, we hypothesise that activation of RIG-I-like receptors (RLR) by endogenous nucleic acid ligands released during mechanical stress is involved in the calcification of the aorta. RLRs are ubiquitously expressed cytoplasmic helicases which trigger innate antiviral responses characterised by type I IFN-inducible genes. Collectively, the results from the first funding period strongly support the critical role of RLRs in the pathogenesis of aortic calcification. In the next funding period, we aim to i) identify RLR-associated therapeutic targets, ii) study the involvement of the cGAS-Sting pathway, iii) dissect the cellular and subcellular source of endogenous RLR- and cGAS ligands, iv) study the impact of mechanical stress-induced actin cytoskeleton remodelling and v) will finally apply an advanced therapeutic antisense approach to confirm molecular targets in vivo.