SIRT1: A novel antithrombotic target in cardiovascular disease? (Miss María Rosario Blanco López)

Platelets play a pivotal role in atherothrombosis, with antiplatelet agents providing important reduction in clinical events.

However, adverse bleeding and variable patient responses limit the safety and efficacy of current strategies, necessitating the development of novel approaches.

SIRT1 is an NAD+ dependent deacetylase, which has recently gained attention for its protective effects against cellular damage.

Reduced SIRT1 levels are linked with diseases including metabolic syndrome and cardiovascular disease, resulting in ongoing clinical trials of SIRT1 activators for a range of pathologies. The importance of SIRT1 in regulating platelet activation and thrombus formation however is unknown. Our preliminary data has shown that, SIRT1 is present in platelets and negatively regulates platelet aggregation.

We have also shown that circulating SIRT1 levels are reduced in patients with type 2 diabetes, who typically have increased platelet reactivity.

In this study, we will define the role of SIRT1 in regulating thrombopoeisis, platelet function and thrombus formation, and characterize the signalling pathways responsible. We will also delineate the effects of SIRT1 activators on the antithrombotic capacity of endothelial cells.

These data will provide a comprehensive overview of the antithrombotic potential of SIRT1 activators and indicate whether SIRT1 activators, could be repurposed as novel antithrombotic agents