Atherosclerosis is an inflammatory condition and the main cause of CVD, initiated by retention of cholesterol in the vessel wall, and leading to the 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 (TNF-related apoptosis-inducing ligand) is produced by most cells in the body. Intriguingly, low TRAIL levels independently predict cardiovascular events and mortality, and 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, and how TRAIL’s protective actions in atherosclerosis relate to its role in monocytes and macrophages.