Atherosclerosis – A matter of unresolved inflammation

• Unstable atherosclerotic lesions show typical features of failed resolution.
• Disturbances in leukocyte accumulation, macrophage polarization, and efferocytosis lead to failed resolution.
• Continued recruitment, proliferation, and failed egress lead to leukocyte accumulation.
• Efferocytosis triggers proresolution signals (TGFβ, IL10) and decreases plaque size.
• Resolution-inducing therapies may lead to plaque stabilization.

Atherosclerosis is commonly looked upon as a chronic inflammatory disease of the arterial wall arising from an unbalanced lipid metabolism and a maladaptive inflammatory response. However, atherosclerosis is not merely an inflammation of the vessel wall. In fact, the cardinal signs of unstable atherosclerotic lesions are primarily characteristics of failed resolution of a chronic inflammation. In contrast to acute inflammatory events which are typically self-limiting, atherosclerosis is an unresolved inflammatory condition, lacking the switch from the pro-inflammatory to the pro-resolving phase, the latter characterized by termination of inflammatory cell recruitment, removal of inflammatory cells from the site of inflammation by apoptosis and dead cell clearance, reprogramming of macrophages toward an anti-inflammatory, regenerative phenotype, and finally egress of effector cells and tissue regeneration. Here we present an overview on mechanisms of failed resolution contributing to atheroprogression and deliver a summary of novel therapeutic strategies to restore resolution in inflamed arteries.