Role of pyroptosis in atherosclerosis and its therapeutic implications

J Cell Physiol. 2021 Oct;236(10):7159-7175. doi: 10.1002/jcp.30366. Epub 2021 Mar 23.

Abstract

Atherosclerosis is a significant cardiovascular burden and a leading cause of death worldwide, recognized as a chronic sterile inflammatory disease. Pyroptosis is a novel proinflammatory regulated cell death, characterized by cell swelling, plasma membrane bubbling, and robust release of proinflammatory cytokines (such as interleukin IL-1β and IL-18). Mounting studies have addressed the crucial contribution of pyroptosis to atherosclerosis and clarified the candidate therapeutic agents targeting pyroptosis for atherosclerosis. Herein, we review the initial characterization of pyroptosis, the detailed mechanisms of pyroptosis, current evidence about pyroptosis and atherosclerosis, and potential therapeutic strategies that target pyroptosis in the development of atherosclerosis.

Keywords: GSDMD; NLRP3; anti-inflammatory treatment; atherosclerosis; caspase-1; inflammation; pyroptosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Arteries / drug effects*
  • Arteries / metabolism
  • Arteries / pathology
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Cytokines / metabolism*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Humans
  • Inflammasomes / metabolism*
  • Inflammation Mediators / metabolism*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Myocytes, Smooth Muscle / pathology
  • Pyroptosis / drug effects*
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammasomes
  • Inflammation Mediators