Lipid-laden foam cells in the pathology of atherosclerosis: shedding light on new therapeutic targets

Expert Opin Ther Targets. 2023 Jul-Dec;27(12):1231-1245. doi: 10.1080/14728222.2023.2288272. Epub 2023 Dec 30.

Abstract

Introduction: Lipid-laden foam cells within atherosclerotic plaques are key players in all phases of lesion development including its progression, necrotic core formation, fibrous cap thinning, and eventually plaque rupture. Manipulating foam cell biology is thus an attractive therapeutic strategy at early, middle, and even late stages of atherosclerosis. Traditional therapies have focused on prevention, especially lowering plasma lipid levels. Despite these interventions, atherosclerosis remains a major cause of cardiovascular disease, responsible for the largest numbers of death worldwide.

Areas covered: Foam cells within atherosclerotic plaques are comprised of macrophages, vascular smooth muscle cells, and other cell types which are exposed to high concentrations of lipoproteins accumulating within the subendothelial intimal layer. Macrophage-derived foam cells are particularly well studied and have provided important insights into lipid metabolism and atherogenesis. The contributions of foam cell-based processes are discussed with an emphasis on areas of therapeutic potential and directions for drug development.

Exert opinion: As key players in atherosclerosis, foam cells are attractive targets for developing more specific, targeted therapies aimed at resolving atherosclerotic plaques. Recent advances in our understanding of lipid handling within these cells provide insights into how they might be manipulated and clinically translated to better treat atherosclerosis.

Keywords: Foam cells; atheroma; atherosclerosis; autophagy; cholesterol; efferocytosis; lipoproteins; plaque; therapeutics.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Atherosclerosis* / drug therapy
  • Foam Cells / metabolism
  • Foam Cells / pathology
  • Humans
  • Lipoproteins
  • Macrophages / metabolism
  • Plaque, Atherosclerotic* / drug therapy
  • Plaque, Atherosclerotic* / pathology

Substances

  • Lipoproteins