Atherosclerosis is an inflammatory condition and the main cause of cardiovascular disease (CVD), initiated by retention of cholesterol in the vessel wall, resulting in recruitment and differentiation of monocytes into macrophages. Discovering new pathways that modulate the resolution of inflammation by affecting monocyte/macrophage phenotype could uncover new strategies for treatment of CVD.
TRAIL was originally identified as a cancer-killing cytokine. Intriguingly, low TRAIL levels independently predict cardiovascular events and mortality; circulating TRAIL levels are reduced in patients with CVD. Importantly, our murine models with TRAIL deletion have the same symptoms as CVD patients. Why TRAIL levels and expression are reduced with atherosclerosis are presently unknown. This project seeks to investigate the function of TRAIL, with particular focus on how TRAIL’s protective actions in atherosclerosis relate to its role in monocytes/macrophages.