Involvement of CXCR4/CXCL12 Axis in Atherosclerosis and Arterial Injury

Cell typeCell type–specific functions
MacrophagesUpregulation of CXCR4 by stimulation with oxidized low-density lipoprotein/statins/hypoxia/vascular injury
→Chemotaxis and enhanced macropinocytosis, modulation of inflammatory phenotype
B and T cellsB-cell development and CXCR4-mediated chemotaxis
→Pro-/antiatherogenic effects (phenotype-dependent)
NeutrophilsCXCR4-maintained homeostasis
CXCR4-regulated neutrophil activation
PlateletsCXCR4-regulated amplification of platelet activation and platelet survival
Endothelial cellsUpregulation of CXCR4 by vascular endothelial growth factor/hypoxia/shear stress
CXCL12/CXCR4 axis–mediated angiogenesis
→Both detrimental effects (e.g., plaque neovascularization) and protective effects (e.g., preservation of endothelial barrier function, reendothelialization)
Vascular smooth muscle cellsCXCL12/CXCR4 axis–mediated proliferation and migration
CXCR4 upregulation in injured arterial wall contributing to intimal hyperplasia
→Both detrimental effects (e.g., neointimal hyperplasia) and protective effects (e.g., sustaining contractile phenotype, plaque stabilization by fibrous cap formation)
  • Modified from (1,23,24).