Pathological vascular remodeling is the underlying cause of atherosclerosis and abdominal aortic aneurysm (AAA). Here, we analyzed the role of galectin-1 (Gal-1), a β-galactoside–binding protein, as a therapeutic target for atherosclerosis and AAA. Mice lacking Gal-1 ( Lgals1 −/− ) developed severe atherosclerosis induced by pAAV/D377Y-mPCSK9 adenovirus and displayed higher lipid levels and lower expression of contractile markers of vascular smooth muscle cells (VSMCs) in plaques than wild-type mice. Proteomic analysis of Lgals1 −/− aortas showed changes in markers of VSMC phenotypic switch and altered composition of mitochondrial proteins. Mechanistically, Gal-1 silencing resulted in increased foam cell formation and mitochondrial dysfunction in VSMCs, while treatment with recombinant Gal-1 (rGal-1) prevented these effects. Furthermore, rGal-1 treatment attenuated atherosclerosis and elastase-induced AAA, leading to higher contractile VSMCs in aortic tissues. Gal-1 expression decreased in human atheroma and AAA compared to control tissue. Thus, Gal-1–driven circuits emerge as potential therapeutic strategies in atherosclerosis and AAA.

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Key Points α4β1 integrin and VEGFR2 function as a receptor complex for VEGF in CLL cells. Contribution to VEGF functions in CLL is a novel pathological role for α4β1 integrin in this malignancy.