Anti-Galectin-2 antibody treatment reduces atherosclerotic plaque size and alters macrophage polarity

Jamie Kane, Matthijs Jansen, Sebastian Hendrix, Laura A Bosmans, Linda Beckers, Claudia van Tiel, Marion Gijbels, Noam Zelcer, Carlie J de Vries, Philipp von Hundelshausen, Marc Vervloet, Ed Eringa, Anton Horrevoets, Niels van Royen, Esther Lutgens

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Galectins have numerous cellular functions in immunity and inflammation. Short-term galectin-2 blockade in ischaemia-induced arteriogenesis shifts macrophages to an anti-inflammatory phenotype and improves perfusion. Galectin-2 may also affect other macrophage related cardiovascular diseases. This study aims to elucidate the effects of Galectin-2 inhibition in atherosclerosis. ApoE -/- mice were given a high cholesterol diet (HCD) for 12 weeks. After six weeks of HCD, intermediate atherosclerotic plaques were present. To study the effects of anti-Gal2 nanobody treatment on the progression of existing atherosclerosis, treatment with two llama derived anti-Gal2 nanobodies (clones- 2H8 and 2C10), or vehicle was given for the remaining 6 weeks. Galectin-2 inhibition reduced the progression of existing atherosclerosis. Atherosclerotic plaque area in the aortic root was decreased, especially so in mice treated with 2C10 nanobodies. This clone reduced atherosclerosis severity as reflected by a decrease in fibrous cap atheromas in addition to decreases in plaque size. The number of plaque resident macrophages was unchanged, however, there was a significant increase in the fraction of CD206+ macrophages. 2C10 treatment also increased plaque α-smooth muscle content, and Gal-2 may have a role in modulating the inflammatory status of smooth muscle cells. Remarkably, both treatments reduced serum cholesterol concentrations including reductions in VLDL, LDL, and HDL whilst triglyceride concentrations were unchanged. Prolonged treatment with anti-Gal-2 nanobodies reduced plaque size, slowed plaque progression, and modified the phenotype of plaque macrophages toward an anti-inflammatory profile. These results hold promise for future macrophage modulating therapeutic interventions that promote arteriogenesis and reduce atherosclerosis.

Original languageEnglish
Pages (from-to)1047-1057
Number of pages11
JournalThrombosis and Haemostasis
Volume122
Issue number06
Early online date1 Dec 2021
DOIs
Publication statusPublished - Jun 2022

Keywords

  • nanobodies
  • anti-inflammatory agents
  • atherosclerosis
  • galectin-2
  • macrophages
  • HUMAN GALECTIN-2
  • ARTERY-DISEASE
  • APOPTOSIS
  • ABCA1
  • TRANSPORTERS
  • CHOLESTEROL

Cite this