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Chronic inflammation and vascular cell plasticity in atherosclerosis

Nature Cardiovascular Research volume 3, pages 1408–1423 (2024)Cite this article

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Abstract

Vascular smooth muscle cells, endothelial cells and macrophages undergo phenotypic conversions throughout atherosclerosis progression, both as a consequence of chronic inflammation and as subsequent drivers of it. The inflammatory hypothesis of atherosclerosis has been catapulted to the forefront of cardiovascular research as clinical trials have shown that anti-inflammatory therapy reduces adverse cardiovascular events. However, no current therapies have been specifically designed to target the phenotype of plaque cells. Fate mapping has revealed that plaque cells convert to detrimental and beneficial cell phenotypes during atherosclerosis, with cumulative evidence highlighting that vascular cell plasticity is intimately linked with plaque inflammation, ultimately impacting lesion stability. Here we review vascular cell plasticity during atherosclerosis in the context of the chronic inflammatory plaque microenvironment. We highlight the need to better understand how plaque cells behave during therapeutic intervention. We then propose modulating plaque cell phenotype as an unexplored therapeutic paradigm in the clinical setting.

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Fig. 1: Historical timeline of key discoveries in studies investigating inflammation and vascular cell plasticity in atherosclerosis.
Fig. 2: Inflammation and vascular cell plasticity during atherosclerosis progression.
Fig. 3: Vascular cell plasticity is affected by some therapeutic treatments.
Fig. 4: Potential therapeutic strategies for resolving inflammation and improving the vascular cell phenotype in atherosclerosis.

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Acknowledgements

A.M. is supported by a Heart Foundation Vanguard grant (NHF1017) and a New South Wales Cardiovascular Research Capacity Program grant (DOH1024). E.A.F. is supported by a National Heart, Lung and Blood Institute grant (National Institutes of Health R01HL084312). A.L. is supported by an Australian Government Research Training Program Scholarship.

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Authors and Affiliations

  1. Atherosclerosis and Vascular Remodelling Group, Heart Research Institute, Sydney, New South Wales, Australia

    Alexander Lin & Ashish Misra

  2. School of Biomedical Engineering, Faculty of Engineering, The University of Sydney, Sydney, New South Wales, Australia

    Alexander Lin

  3. Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA

    Joseph M. Miano

  4. Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA

    Edward A. Fisher

  5. Cardiovascular Research Center, New York University Grossman School of Medicine, New York, NY, USA

    Edward A. Fisher

  6. Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia

    Ashish Misra

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Lin, A., Miano, J.M., Fisher, E.A. et al. Chronic inflammation and vascular cell plasticity in atherosclerosis. Nat Cardiovasc Res 3, 1408–1423 (2024). https://doi.org/10.1038/s44161-024-00569-y

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