Effect of Flavonoids on MCP-1 Expression in Human Coronary Artery Endothelial Cells and Impact on MCP-1-Dependent Migration of Human Monocytes

Int J Mol Sci. 2023 Nov 7;24(22):16047. doi: 10.3390/ijms242216047.

Abstract

The monocyte chemoattractant protein-1 (MCP-1), also known as chemokine (CC motif) ligand 2 (CCL2), is involved in the formation, progression, and destabilization of atheromatous plaques. Flavonoids, found in fruits and vegetables, have been associated with various health-promoting properties, including antioxidant, anti-inflammatory, and cardioprotective effects. In the present study, the flavonoids quercetin, kaempferol, and luteolin, but not cannflavin A, were shown to substantially inhibit interleukin (IL)-1β-induced MCP-1 mRNA and protein expression in human coronary artery endothelial cells (HCAEC). At the functional level, conditioned medium (CM) from IL-1β-stimulated HCAEC caused an increase in the migration of THP-1 monocytes compared with CM from unstimulated HCAEC. However, this induction was suppressed when IL-1β-treated HCAEC were coincubated with quercetin, kaempferol, or luteolin. The functional importance of MCP-1 in IL-1β-induced monocyte migration was supported by experiments showing that neutralization of MCP-1 in the CM of IL-1β-treated HCAEC led to a significant inhibition of migration. In addition, a concentration-dependent induction of monocyte migration in the presence of recombinant MCP-1 was demonstrated. Collectively, the flavonoids quercetin, kaempferol, and luteolin were found to exert potential antiatherogenic effects in HCAEC, challenging further studies with these compounds.

Keywords: flavonoids; monocyte chemoattractant protein-1; monocyte migration; vascular endothelial cells.

MeSH terms

  • Cells, Cultured
  • Chemokine CCL2* / metabolism
  • Coronary Vessels / metabolism
  • Endothelial Cells / metabolism
  • Flavonoids / metabolism
  • Flavonoids / pharmacology
  • Humans
  • Immunologic Factors / pharmacology
  • Kaempferols / metabolism
  • Kaempferols / pharmacology
  • Luteolin / pharmacology
  • Monocytes* / metabolism
  • Quercetin / metabolism
  • Quercetin / pharmacology

Substances

  • Chemokine CCL2
  • Kaempferols
  • Flavonoids
  • Quercetin
  • Luteolin
  • Immunologic Factors

Grants and funding

This research received no external funding.