The intracellular signalling pathways governing macrophage activation and function in human atherosclerosis

Heather M Wilson* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)
3 Downloads (Pure)


Atherosclerosis is a chronic inflammatory disease characterized by lipid accumulation and plaque formation in arterial vessel walls. Atherosclerotic plaques narrow the arterial lumen to increase the risk of heart attacks, ischemic stroke and peripheral vascular disease, which are major and worldwide health and economic burdens. Macrophage accumulation within plaques is characteristic of all stages of atherosclerosis and their presence is a potential marker of disease activity and plaque stability. Macrophages engulf lipids and modified lipoproteins to form foam cells that express pro-inflammatory and chemotactic effector molecules, stress inducing factors and reactive oxygen species. They control plaque stability and rupture through secretion of metalloproteinases and extracellular matrix degradation. Although macrophages can worsen disease by propagating inflammation, they can stabilize atherosclerotic plaques through tissue remodeling, promoting the formation of a fibrous cap, clearing apoptotic cells to prevent necrotic core formation and through vascular repair. In atherosclerosis, macrophages respond to dyslipidaemia, cytokines, dying cells, metabolic factors, lipids, physical stimuli and epigenetic factors and exhibit heterogeneity in their activation depending on the stimuli they receive. Understanding these signals and the pathways driving macrophage function within developing and established plaques and how they can be pharmacologically modulated, represents a strategy for the prevention and treatment of atherosclerosis. This review focusses on the current understanding of factors controlling macrophage heterogeneity and function in atherosclerosis. Particular attention is given to the macrophage intracellular signaling pathways and transcription factors activated by biochemical and biophysical stimuli within plaques, and how they are integrated to regulate plaque formation and stability.

Original languageEnglish
Article numberBST20220441
Pages (from-to)1673–1682
Number of pages10
JournalBiochemical Society Transactions
Issue number6
Early online date23 Nov 2022
Publication statusPublished - Dec 2022

Bibliographical note

Acknowledgements: Thanks to Dr Dawn Thompson, University of Aberdeen for
critically reviewing the article
HMW acknowledges funding from British Heart Foundation (PG/19/30/34327) and NHS Grampian Endowments (21/001).


  • atherosclerosis
  • macrophages
  • intracellular signaling
  • inflammation


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