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 J. Horrevoets, Niels Van Royen, Esther Lutgens

Research output: Contribution to journalArticlepeer-review


Background  Galectins have numerous cellular functions in immunity and inflammation. Short-term galectin-2 (Gal-2) blockade in ischemia-induced arteriogenesis shifts macrophages to an anti-inflammatory phenotype and improves perfusion. Gal-2 may also affect other macrophage-related cardiovascular diseases. Objectives  This study aims to elucidate the effects of Gal-2 inhibition in atherosclerosis. Methods   ApoE -/-mice were given a high-cholesterol diet (HCD) for 12 weeks. After 6 weeks of HCD, intermediate atherosclerotic plaques were present. To study the effects of anti-Gal-2 nanobody treatment on the progression of existing atherosclerosis, treatment with two llama-derived anti-Gal-2 nanobodies (clones 2H8 and 2C10), or vehicle was given for the remaining 6 weeks. Results  Gal-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 showed 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 very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein while triglyceride concentrations were unchanged. Conclusion  Prolonged and frequent 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 (US)
Pages (from-to)1047-1057
Number of pages11
JournalThrombosis and Haemostasis
Issue number6
StatePublished - Feb 8 2022


  • anti-inflammatory agents
  • atherosclerosis
  • galectin-2
  • macrophages
  • nanobodies

ASJC Scopus subject areas

  • Hematology


Dive into the research topics of 'Anti-Galectin-2 Antibody Treatment Reduces Atherosclerotic Plaque Size and Alters Macrophage Polarity'. Together they form a unique fingerprint.

Cite this