Project abstract

Lipid lowering has significantly reduced cardiovascular disease (CVD) mortality in EU. However, the aim to abolish CVD in EU is far from achieved and attempts to improve on the benefits of statins with new agents have not yet delivered new therapeutics. The Consortium Athero-Flux builds on FP7-generated large-scale lipidomics data showing that specific sphingolipids (SLs) with specific acyl chain lengths are better predictors of CV outcome than traditional risk factors such as low-density lipoprotein-cholesterol.

SLs are implicated in significant biological activities including cell survival, inflammation, and metabolic  diseases. Moreover, their levels in metabolic diseases are modulated by previously unrecognized factors such as the gut microflora. Thus, we hypothesize that by controlling SL metabolism a better primary and secondary prevention of CVD events than with statins alone can be achieved.

Athero-Flux builds on cutting-edge SME-led biotechnological tools including: a) high-throughput lipidomic platforms that allow the study of kinetics of lipid metabolism at the molecular lipid level including the new stable isotope labelling technique (Flux); b) whole genome RNA interference screening tools that will allow to identify the regulators of the production of SLs and the mediators of their biological effect; c) unique locked nucleotide antagonist platforms that have been successfully used clinically in more than 300 patients worldwide. The identification and the validation of the best targets to abate SL metabolism though a combination of SME-based leading technology and academia modeling has a strong potential for development of new lipid lowering therapeutics to abate previously unrecognized risk factors for CVD.

This project is supported through Coordination Theme 1 (Health) of the
European Community's FP7. Grant agreement number HEALTH-F2-2013-602222