Defining the molecular mechanisms underpinning inflammatory regulation of the vasculature

This project will investigate the utility of novel anti-inflammatory compounds in the regulation of the cardiovascular system. Cardiovascular disease (CVD) remains the leading cause of death worldwide, number 1 in Scotland and it is now widely accepted that chronic inflammation is a major driver of disease progression. Previous attempts to inhibit the inflammatory response have resulted in an increased susceptibility to infection. Hence, understanding the molecular mechanisms underlying inflammation regulation and its contribution to CVD is therefore critical to well-being and for the development of more effective therapies.
Specifically, this study will investigate the molecular processes engaged by activation of the 'highly druggable' formyl peptide receptor 2 (FPR2). Research has shown FPR2 is essential in controlling the switch from pro-inflammation to pro-resolution signalling to enable tissue healing and, as such, has been proposed as a potential candidate for the development of novel therapeutics targeting chronic inflammation. Excitingly, our recent work has uncovered new insight, indicating endocytic trafficking of FPR2 is critical for the resolution of inflammation. We have discovered disruption of FPR2 trafficking increased cellular apoptosis; reported as a key requirement for resolution. This finding provides a novel molecular target for understanding inflammation and the development of therapeutics. Finally, the consequences of FPR2 stimulation is ligand-specific and can determine whether signalling is beneficial or detrimental. However, the molecular mechanisms defining these opposing physiological outcomes are poorly understood. This study will elucidate these processes.