Project Title

STINGing Away Atherosclerosis: The Role of IFN-Driven Endothelial Activity 

Background

Lipid-lowering therapies reduce ASCVD incidence, but unresolved inflammation sustains residual risk. While inflammation research has traditionally focused on immune cells, ECs are now recognized as critical contributors to disease progression. We recently discovered that ECs exhibit unexpected immunomodulatory properties, displaying a robust IFN-I signature upon STING activation—a response typically associated with immune cells. 

Aim

Building on these findings, we aim to explore the potential of targeting the endothelial STING-IFN-I pathway as a novel anti-inflammatory strategy to further reduce ASCVD incidence. 

Methods

To elucidate the role of the endothelial STING-IFN-I pathway in atherosclerosis, we will use unique EC-specific knockout mouse models developed in-house. Additionally, to assess the therapeutic potential of targeting this pathway, we will design nanoparticles for EC-targeted inhibition of STING-IFN-I signalling. 

Preliminary results

Our recent in vitro studies confirmed that STING activation in ECs triggers IFN-I signalling, leading to an inflamed EC phenotype characterized by upregulated VCAM-1 and ICAM-1 expression and increased secretion of the proinflammatory cytokine CXCL10. These findings underscore the pivotal role of the STING–IFN-I pathway in driving endothelial inflammation. 

Perspectives

This project will uncover novel inflammatory pathways governing atherosclerosis development, potentially identifying highly effective therapeutic targets for preventing and treating cardiovascular diseases. By targeting endothelial-specific mechanisms, we aim to advance the development of precision anti-inflammatory therapies that address the unresolved burden of ASCVD.