Athero-Flux · Targeting novel lipid pathways for treatment of cardiovascular disease

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 and in particular distinct ceramides with specific acyl chain lengths are better predictors of CV outcome than traditional risk factors such as low-density lipoprotein-cholesterol. Sphingolipids 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 sphingolipid 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 ceramides and the mediators of their biological effect; c) unique locked nucleotide antagonist platforms that have been successfully used clinically in more that 300 patients worldwide. Moreover, it involves Academic partners with top expertise in atherosclerosis, sphingolipid metabolism, and gut microflora to validate targets in the ceramide metabolism. The identification and the validation of the best targets to abate ceramide 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.