Roldán-Montero, RaquelPérez-Sáez, Juan MCerro-Pardo, IsabelOller, JorgeMartinez-Lopez, DiegoNunez, EstefaniaMaller, Sebastian MGutierrez-Muñoz, CarmenMendez-Barbero, NereaEscola-Gil, Joan CMichel, Jean-BaptisteMittelbrunn, MariaVazquez, JesusBlanco-Colio, Luis MRabinovich, Gabriel AMartin-Ventura, Jose L2022-12-092022-12-092022-03-18Sci Adv. 2022 Mar 18;8(11):eabm7322http://hdl.handle.net/20.500.12105/15264Pathological 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.engVoRhttp://creativecommons.org/licenses/by/4.0/Aortic Aneurysm, AbdominalAtherosclerosisAnimalsDisease Models, AnimalGalectin 1MiceMice, Inbred C57BLMuscle, Smooth, VascularProteomicsVascular RemodelingAtribución 4.0 Internacional35294231811eabm732210.1126/sciadv.abm73222375-2548Science advancesopen access