Galectin-9: A novel promoter of atherosclerosis progression
Franziska Krautter, Mohammed T. Hussain, Zhaogong Zhi, Danielle Lezama, Julia E. Manning, Emily J. Brown, Noemi Marigliano, Federica Raucci, Carlota Recio, Myriam Chimen, Francesco Μaione, Alok Tiwari, Helen M. McGettrick, Dianne Cooper, Edward A. Fisher, Asif Iqbal
Abstract
BACKGROUND AND AIMS: Atherosclerosis is widely accepted to be an inflammatory disease driven by lipid accumulation and leukocyte recruitment. More recently, galectins, a family of β-galactoside binding proteins, have been shown to play a role in leukocyte recruitment among other immunomodulatory functions. Galectin (Gal) -9, a tandem repeat type galectin expressed by the endothelium in inflammatory environments, has been proposed to promote leukocyte recruitment. However, the role of Gal-9 in the context of monocyte recruitment remains elusive. METHODS AND RESULTS: monocytes in a β2-integrin and glycan dependent manner, while adhesion of monocytes to stimulated endothelium is reduced when Gal-9 is knocked down. Gal-9 also facilitates enhanced recruitment of leukocytes from peripheral arterial disease (PAD) patients compared to healthy young and aged controls. We further characterise the endothelium as source of circulating Gal-9, which is increased in plasma of PAD patients compared to healthy controls. CONCLUSIONS: These results highlight a pathological role for Gal-9 as promoter of monocyte recruitment and atherosclerotic plaque progression, making it a novel target in the prevention of plaque formation and progression.