LAUSR

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.