Galectin-1 prevents pathological vascular remodeling in atherosclerosis and abdominal aortic aneurysm

RAQUEL ROLDÁN-MONTERO; JUAN M. PÉREZ-SÁEZ; ISABEL CERRO-PARDO; JORGE OLLER; DIEGO MARTINEZ-LOPEZ; ESTEFANIA NUÑEZ; SEBASTIAN M. MALLER; CARMEN GUTIERREZ-MUÑOZ; NEREA MENDEZ-BARBERO; JOAN C. ESCOLA-GIL; JEAN-BAPTISTE MICHEL; MARIA MITTELBRUNN; JESÚS VÁZQUEZ; LUIS M. BLANCO-COLIO; GABRIEL A. RABINOVICH* (CO-SENIOR); JOSE L. MARTIN-VENTURA* (* CO-SENIORS)

Science Advances

Science Advances is the American Association for the Advancement of Science

Año: 2022

2375-2548

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 -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 musclecells (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.