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Author
Krautter, FranziskaHussain, Mohammed T
Zhi, Zhaogong
Lezama, Danielle R
Manning, Julia E
Brown, Emily
Marigliano, Noemi
Raucci, Federica
Recio, Carlota
Chimen, Myriam
Maione, Francesco
Tiwari, Alok
McGettrick, Helen M
Cooper, Dianne
Fisher, Edward A
Iqbal, Asif J
Publication date
2022-11-19
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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: Here, we characterise the immunomodulatory role of Gal-9 in context of atherosclerosis. We show that ApoE-/-Gal-9-/- mice have a significantly reduced aortic plaque burden compared to their ApoE-/- littermate controls after 12 weeks of high fat diet. RNA sequencing data from two independent studies reveal Lgals9 expression in leukocyte clusters isolated from murine atherosclerotic plaques. Additionally, soluble Gal-9 protein induces monocyte activation and a pro-inflammatory phenotype in macrophages. Furthermore, we show that immobilised recombinant Gal-9 acts as capture and adhesion molecule for CD14+ 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.Citation
Krautter F, Hussain MT, Zhi Z, Lezama DR, Manning JE, Brown E, Marigliano N, Raucci F, Recio C, Chimen M, Maione F, Tiwari A, McGettrick HM, Cooper D, Fisher EA, Iqbal AJ. Galectin-9: A novel promoter of atherosclerosis progression. Atherosclerosis. 2022 Dec;363:57-68. doi: 10.1016/j.atherosclerosis.2022.11.014. Epub 2022 Nov 19Type
ArticleAdditional Links
https://www.sciencedirect.com/journal/atherosclerosisPMID
36459823Journal
AtherosclerosisPublisher
Elsevierae974a485f413a2113503eed53cd6c53
10.1016/j.atherosclerosis.2022.11.014