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Atherosclerosis resolution: strategies to remodel and resolve plaques
Emily Halbedl1, Edward A Fisher
1Department of Medicine, Leon H. Charney Division of Cardiology, Cardiovascular Research Center, New York University Grossman School of Medicine, New York, New York, USA.
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.
Insights
Atherosclerosis resolution involves plaque remodeling, not just size reduction. Targeting inflammation alongside cholesterol lowering offers a promising strategy for reducing residual cardiovascular risk.
Area of Science:
- Cardiovascular Research
- Inflammation Biology
- Atherosclerosis Pathogenesis
Background:
- Residual cardiovascular risk persists despite aggressive lipid lowering.
- Atherosclerosis progression is linked to chronic inflammation within plaques.
- Novel strategies are needed to address remaining cardiovascular events.
Purpose of the Study:
- To review recent advances in atherosclerosis resolution research.
- To highlight the role of plaque inflammation in cardiovascular risk.
- To evaluate therapeutic strategies targeting inflammation.
Main Methods:
- Analysis of preclinical atherosclerosis models.
- Evaluation of lipid-lowering and inflammation-targeting pathways.
- Review of translational studies and clinical trials on inflammatory mediators.
Main Results:
- Atherosclerosis resolution involves plaque remodeling (necrotic core, CD68 area, collagen content), not solely size reduction.
- Combination approaches of lipid lowering and inflammation resolution are effective.
- Targeting inflammatory pathways (e.g., IL-1β, IL-6, NLRP3) shows therapeutic potential.
Conclusions:
- Preclinical models demonstrate plaque remodeling via lipid lowering, inflammation resolution, or combined approaches.
- Clinical trials are investigating inflammation resolution to reduce cardiovascular risk.
- Modulating inflammation is a key strategy for managing residual cardiovascular risk.
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