Macrophage death and defective inflammation resolution in atherosclerosis

An important aspect of atherosclerosis is the defective resolution of the inflammatory response to subendothelial lipoproteins. But what are the pathways involved in inflammation resolution, why are they defective in atherosclerotic lesions and how can they be therapeutically targeted? A key event in atherosclerosis is a maladaptive inflammatory response to subendothelial lipoproteins. A crucial aspect of this response is a failure to resolve inflammation, which normally involves the suppression of inflammatory cell influx, effective clearance of apoptotic cells and promotion of inflammatory cell egress. Defects in these processes promote the progression of atherosclerotic lesions into dangerous plaques, which can trigger atherothrombotic vascular disease, the leading cause of death in industrialized societies. In this Review I provide an overview of these concepts, with a focus on macrophage death and defective apoptotic cell clearance, and discuss new therapeutic strategies designed to boost inflammation resolution in atherosclerosis.