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Atherosclerosis: Insights into Vascular Pathobiology and Outlook to Novel Treatments

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Abstract

The pathobiology of atherosclerosis and its current and potential future treatments are summarized, with a spotlight on three central cell types involved: (i) endothelial cells (ECs), (ii) macrophages, and (iii) vascular smooth muscle cells (VSMCs). (i) EC behaviour is regulated by the central transcription factors YAP/TAZ in reaction to biomechanical forces, such as hemodynamic shear stress. (ii) VSMC transdifferentiation (phenotype switching) to a macrophage-like phenotype contributes to the majority of cells positive for common cell surface macrophage markers in atherosclerotic plaques. (iii) Intra-plaque macrophages originate in a significant number from vascular resident macrophages. They can be activated via pattern recognition receptors on cell membrane (e.g. toll-like receptors) and inside cells (e.g. inflammasomes), requiring priming by neutrophil extracellular traps (NETs). ECs and macrophages can also be characterized by single-cell RNA sequencing. Adaptive immunity plays an important role in the inflammatory process. Future therapeutic options include vaccination, TRAF-STOPs, senolysis, or CD47 blockade.

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Funding

This this study was funded by the Swiss National Science Foundation research program NRP 62 ‘Smart Materials’ and the Basler Herzstiftung.

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Authors and Affiliations

  1. Nanomedicine Research Lab CLINAM, University Hospital Basel, University of Basel, Bernoullistrasse 20, CH-4056, Basel, Switzerland

    Marc P. Wolf & Patrick Hunziker

  2. CLINAM Foundation for Clinical Nanomedicine, Alemannengasse 12, CH-4016, Basel, Switzerland

    Patrick Hunziker

Authors
  1. Marc P. Wolf
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  2. Patrick Hunziker
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Correspondence to Marc P. Wolf.

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Wolf, M.P., Hunziker, P. Atherosclerosis: Insights into Vascular Pathobiology and Outlook to Novel Treatments. J. of Cardiovasc. Trans. Res. 13, 744–757 (2020). https://doi.org/10.1007/s12265-020-09961-y

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  • DOI: https://doi.org/10.1007/s12265-020-09961-y

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