Atherosclerosis resolution: strategies to remodel and resolve plaques

PURPOSE OF REVIEW: Despite aggressive cholesterol lowering, many patients continue to experience cardiovascular events ("residual risk"), emphasizing the need for novel risk reduction strategies. This review highlights recent advances in studying atherosclerosis resolution, with a focus on the key role played by plaque inflammation. RECENT FINDINGS: Preclinical studies demonstrate that while atherosclerosis resolution can involve plaque size reductions, more important are changes in plaque remodeling, as measured by necrotic core, CD68 area, and collagen content. Resolution can be partially achieved with cholesterol lowering, inflammation resolution alone, or better yet, combination approaches. This review evaluates lipid-lowering strategies, as well as inflammation-targeting pathways involving efferocytosis, pro-resolving macrophages, platelets, and caloric restriction. Translational studies and clinical trials targeting inflammatory pathways, including interleukin (IL)-1β, IL-6, NLRP3, and pro-resolving mediators further support inflammation modulation as a therapeutic strategy. SUMMARY: Many preclinical models of atherosclerosis resolution promote significant plaque remodeling by lipid-lowering, inflammation resolution, or combination approaches. Many recent and currently recruiting clinical trials are testing the benefits of inflammation resolution to further reduce cardiovascular risk in at-risk patients.